Mol Imaging Biol [JOURNAL]
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200 papers
I-Labeled Specific Antibody Targeting LAG-3 for ImmunoPET.
Ding L, Wang F, Pan Y … +6 more , Liu W, Cheng L, Tuo F, Ding K, Zhu H, Yang Z
Mol Imaging Biol · 2026 Feb · PMID 41430028 · Publisher ↗
PURPOSE: Lymphocyte-activation gene 3 (LAG-3), a next-generation immune checkpoint, has emerged as a promising therapeutic target, but noninvasive tools for evaluating LAG-3 expression remain limited. Herein, we explored...
PURPOSE: Lymphocyte-activation gene 3 (LAG-3), a next-generation immune checkpoint, has emerged as a promising therapeutic target, but noninvasive tools for evaluating LAG-3 expression remain limited. Herein, we explored an antibody-dependent molecular imaging strategy for noninvasive detection based on a LAG-3-specific antibody, HuL13. PROCEDURES: The anti-LAG-3 antibody HuL13 was radiolabeled with I via electrophilic substitution. LAG-3-expressing A549 cells were constructed by infection with the lentivirus. The specificity and affinity of I-HuL13 to LAG-3 receptor were evaluated by cell uptake assay and saturation binding assay. Micro-PET/CT imaging studies were conducted in BALB/c nude mice bearing LAG-3 A549 tumors. Immunohistochemistry (IHC) validated LAG-3 expression in tumors. RESULTS: The I-HuL13 exhibited a good radiochemical yield of 95.59 ± 1.27%, high radiochemical purity (RCP, > 99%), and excellent stability. Cell binding assays demonstrated that I-HuL13 had a higher binding ability to LAG-3 A549 cells compared to control cells. The equilibrium dissociation constant (Kd) of I-HuL13 was 23.02 nM for LAG-3 A549 cells. In vivo pharmacokinetics revealed favorable metabolic stability (t = 12.07 h). Micro-PET/CT images showed that I-HuL13 significantly accumulated in LAG-3 A549 tumor from 24 h after injection (SUVmax = 0.34 ± 0.03 at 24 h), and high contrast tumor to background imaging was clearly observed. IHC confirmed LAG-3 expression correlated with probe uptake. CONCLUSIONS: I-HuL13 is a novel LAG-3-targeted PET imaging radiotracer with excellent stability. This study highlights I-HuL13 as a robust tool for noninvasive LAG-3 imaging, offering potential for optimizing LAG-3-targeted immunotherapy in clinical settings.
AMPK Activation by MK-8722 Measured with [F]FDG-PET Imaging in Rodents and Non-Human Primates.
Rubins DJ, Meng X, Wang S … +9 more , Haley H, Posavec D, Purcell M, Riffel K, Myers RW, Sebhat IK, Trotter DG, Klimas M, Holahan M
Mol Imaging Biol · 2026 Feb · PMID 41428151 · Publisher ↗
INTRODUCTION: The adenosine monophosphate-activated protein kinase (AMPK) induces glucose uptake by increasing the expression of glucose transporter 4 (GLUT4), and [F]Fluorodeoxyglucose (FDG) is readily transported into...
INTRODUCTION: The adenosine monophosphate-activated protein kinase (AMPK) induces glucose uptake by increasing the expression of glucose transporter 4 (GLUT4), and [F]Fluorodeoxyglucose (FDG) is readily transported into tissues with high GLUT4 expression. Thus, positron emission tomography with FDG (FDG-PET) could serve as an important pharmacodynamic readout of AMPK activation. In this study, the impact of treatment with the pan-AMPK activator MK-8722 on FDG uptake was evaluated in rats and Rhesus monkeys. METHODS: Rats were evaluated with FDG-PET following intravenous (IV) or oral (PO) administration of MK-8722. Rhesus monkeys were orally dosed and evaluated with FDG-PET. FDG uptake was measured in skeletal and cardiac muscle, and the incorporation rate was calculated using the Patlak graphical method. RESULTS: In rats, the highest IV dose of MK-8722 (5 mg/kg) and both PO doses (4 mg/kg and 10 mg/kg) given 4 h prior to FDG-PET resulted in a significant increase in forelimb skeletal muscle FDG uptake (p < 0.01). In Rhesus monkeys, chronic oral administration of 10 mg/kg MK-8722 QD resulted in significantly higher FDG uptake in bicep skeletal muscle than vehicle treatment after 2 and 4 weeks of treatment (p < 0.01), but no difference was observed after 5 weeks of drug washout (p > 0.05). FDG uptake in cardiac muscle was significantly reduced with MK-8722 treatment in rats, but no significant changes in cardiac muscle FDG uptake were measured in Rhesus monkey. CONCLUSIONS: FDG-PET can be used as a pharmacodynamic readout for systemic pharmacological activation of AMPK for preclinical studies and potentially be extended to study humans.
Identification of a Novel TIM-3 Targeting Peptides Probe to Indicate the Immunomodulation of SBRT Combined with Anti-TIM-3 Therapy in HCC.
Xu M, Wang C, Zeng P … +6 more , An Y, Qin Y, Wu M, Zhang J, Lu Q, Chen R
Mol Imaging Biol · 2026 Feb · PMID 41392062 · Publisher ↗
PURPOSE: Given the escalating global burden and high mortality associated with hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) have emerged as a critical therapeutic approach. T cell immunoglobulin an...
PURPOSE: Given the escalating global burden and high mortality associated with hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) have emerged as a critical therapeutic approach. T cell immunoglobulin and mucin-domain containing-3 (TIM-3), an emerging immune checkpoint that is highly expressed in HCC, has been linked to poor prognosis due to its association with exhausted T cells and suppressed immune responses. Anti-TIM-3 therapy may hold potential for activating immunity in HCC patients. Stereotactic body radiotherapy (SBRT), a precise radiation technique, can activate the tumor immunity and modulate IC expression. Therefore, the combination of anti-TIM-3 therapy with SBRT is anticipated to enhance the immune response in HCC. An effective measure to evaluate TIM-3 expression after SBRT for improving the synergistic efficacy is needed. This study aimed to develop a non-invasive tool to monitor TIM-3 expression in HCC and optimize the combination of anti-TIM-3 therapy with SBRT to enhance antitumor efficacy. PROCEDURES: Clinical data and pathological specimens from HCC patients were collected to evaluate TIM-3 expression in tumor tissues via immunohistochemistry (IHC). A 12-amino-acid peptide targeting TIM-3 was screened via phage display technology and subsequently conjugated with a fluorescent moiety to construct a near-infrared fluorescence (NIRF) probe. The probe's targeting capability for TIM-3 imaging and its in vivo biodistribution were evaluated using NIRF imaging. After intravenous administration of the TIM-3-targeted probe to mice, dynamic changes in intratumoral TIM-3 expression under varying radiation doses (0/4/6/8 Gy × 3F) were visualized via longitudinal optical imaging, identifying the optimal radiation regimen for TIM-3 modulation. Splenic cells were isolated for FCM analysis of TIM-3 cell subpopulations post-SBRT. After determineing the optimal radiotherapy dose, therapeutic efficacy was evaluated in four cohorts: SBRT monotherapy, anti-TIM-3 monotherapy, SBRT-anti-TIM-3 combination therapy, and untreated controls. Tumor regression was monitored via bioluminescence imaging, while splenic CD8 T-cell expansion was quantified by FCM to characterize systemic immune activation. RESULTS: TIM-3 was highly expressed in human HCC tissues, with its expression level significantly correlated with tumor stage, vascular invasion status, and patient performance status (PS) score (p < 0.0001). TIM-3 targeting peptides probe was constructed successfully. In vivo fluorescence imaging showed significantly higher tumor-specific fluorescence intensity in mice injected with TIM-3-targeted peptide probe compared to those receiving non-specific probe (p < 0.0001), with peak intratumoral probe accumulation observed at 1 h post-injection. Ex vivo organ imaging confirmed predominant probe biodistribution in the liver and kidneys. Radiation dose-response analysis revealed minimal TIM-3 expression in tumors treated with 6 Gy × 3F SBRT (p < 0.0001), accompanied by significant downregulation of splenic TIM-3 cells (p < 0.01). Notably, the combination therapy group (SBRT + anti-TIM-3) exhibited superior tumor suppression compared to monotherapy cohorts (p < 0.05), as validated by bioluminescence imaging. Flow cytometry further demonstrated a synergistic increase in splenic CD8 T-cell infiltration within the combination group (p < 0.05), indicating enhanced systemic immune activation. CONCLUSIONS: This study provides a novel, real-time method to monitor TIM-3 expression in HCC, offering critical insights into SBRT-induced immunomodulation. The combination of SBRT (at the identified optimal dose) with anti-TIM-3 therapy demonstrates enhanced antitumor efficacy, presenting a translational strategy for HCC immunotherapy.
Evaluation of Pafolacianine (Cytalux) for Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma: A Negative Study with Important Clinical Implications.
Mani L, Zaidi SMA, Martin E … +6 more , Burns CR, Naveed AB, McAdoo A, Tanaka H, Rosenthal E, Hom M
Mol Imaging Biol · 2026 Feb · PMID 41379363 · Full text
BACKGROUND: Pafolacianine (Cytalux) represents the first FDA-approved tumor-specific fluorescence imaging agent, demonstrating efficacy in ovarian cancer through folate receptor-α (FR-α) targeting. Given the need for imp...
BACKGROUND: Pafolacianine (Cytalux) represents the first FDA-approved tumor-specific fluorescence imaging agent, demonstrating efficacy in ovarian cancer through folate receptor-α (FR-α) targeting. Given the need for improved intraoperative margin assessment in head and neck squamous cell carcinoma (HNSCC), where positive surgical margins occur in 10-30% of cases, we investigated the potential utility of pafolacianine for fluorescence-guided surgery in HNSCC models. OBJECTIVE: To evaluate the feasibility of visualizing HNSCC using pafolacianine in vitro, in vivo, and clinical tissue analysis, with comparison to fluorescence-guided surgery agents that have been successful in patients. METHODS: HNSCC cell lines (FaDu, UMSCC47) were treated with escalating concentrations of pafolacianine (0-500 nM) and assessed for binding at 1 and 24 h. Nude mice bearing HNSCC xenografts (FaDu, UMSCC47) received intraperitoneal injection of pafolacianine (10 nmol) with fluorescence imaging at multiple timepoints. Immunohistochemistry analysis of patient samples (n = 8 tumor, n = 8 normal) evaluated FR-α and FR-β expression. Panitumumab-IRDye800CW served as a positive control for comparison. RESULTS: In vitro analysis demonstrated minimal pafolacianine binding across all HNSCC cell lines, with fluorescence intensities similar to or lower than the FR-α-negative A549 control cell line. In vivo imaging revealed poor tumor localization with mean fluorescence intensity (MFI) of 7.39 (FaDu) and 6.97 (UMSCC47), substantially lower than non-target tissues including skin. Immunohistochemistry analysis showed no statistically significant difference in FR-α expression between tumor and normal tissue (p > 0.05). For comparison, panitumumab-IRDye800CW demonstrated robust tumor targeting with MFI of 32.14 (FaDu) and 14.98 (UMSCC47). CONCLUSIONS: This study demonstrates that pafolacianine exhibits limited utility for fluorescence-guided surgery in HNSCC due to insufficient FR-α expression and poor tumor-to-background contrast. These negative findings provide crucial evidence against the clinical translation of pafolacianine for HNSCC applications and highlight the importance of target expression validation in precision medicine approaches. CLINICAL RELEVANCE: Negative studies such as this are essential for evidence-based clinical decision-making, preventing unnecessary resource allocation and potential patient exposure to ineffective interventions. These findings inform the broader fluorescence-guided surgery field and support continued investigation of alternative targeting strategies for HNSCC.
Ethyl Pyruvate Promotes Wound Healing in Elastase-Induced Lung Injury in Mice as Assessed by Hyperpolarized Xe Magnetic Resonance Imaging.
Kimura A, Shimokawa A, Stewart NJ … +3 more , Hosoi R, Imai H, Fujiwara H
Mol Imaging Biol · 2026 Feb · PMID 41372714 · Full text
PURPOSE: Wound healing process in lung injury involves the activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we investigated the role of the MAPK pathway in wound healing in a murine model...
PURPOSE: Wound healing process in lung injury involves the activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we investigated the role of the MAPK pathway in wound healing in a murine model of emphysema using hyperpolarized Xe (HP Xe) magnetic resonance imaging (MRI). PROCEDURES: Porcine pancreatic elastase was administered intratracheally to 25 mice to induce lung injury. Temporal changes in pulmonary gas exchange function were monitored using HP Xe MRI, revealing a significant decline in function one day after elastase administration. Treatments with ethyl pyruvate (EP) and nicorandil (Nic), which upregulate and downregulate the MAPK pathway, respectively, were initiated in 12 and 7 of the 25 mice, respectively, and continued for 20 days. Over the 21-day period, HP Xe MRI was performed to monitor the disease progression and treatment efficacy through changes in the metrics of gas exchange and fractional ventilation. RESULTS: HP Xe MRI showed that EP significantly improved gas exchange function 14 days after elastase administration, whereas Nic did not show any improvement. Ventilatory function also improved in the EP group, but not in the Nic group, 14 days after elastase administration. Histological analysis showed that EP repaired tissue damage to a level similar to that observed in healthy mice, whereas Nic did not. CONCLUSIONS: In the present study, we provide some insight into the role of the MAPK pathway in wound healing in elastase-induced lung injury, as assessed using the HP Xe MRI protocol.
PET Imaging of CD38 and IND enabling studies of [Zr]Zr-DFO-Isatuximab.
Wright BD, Houson HA, Fernandez S … +4 more , Gultekin K, McConathy JE, Giri S, Lapi SE
Mol Imaging Biol · 2026 Feb · PMID 41364284 · Full text
BACKGROUND: CD38 is an excellent biomarker and therapeutic target for multiple myeloma due to its high expression on cancerous cells in comparison to healthy cells. PURPOSE: We aimed to adapt Isatuximab as a PET imaging...
BACKGROUND: CD38 is an excellent biomarker and therapeutic target for multiple myeloma due to its high expression on cancerous cells in comparison to healthy cells. PURPOSE: We aimed to adapt Isatuximab as a PET imaging agent to detect CD38 positive multiple myeloma. METHODS: In vitro studies confirmed the specificity of [Zr]Zr-DFO-Isatuximab in CD38 + OPM-2 and MM.1S cells. Upregulation of CD38 was performed using pomalidomide and ricolinostat. Athymic nude mice were implanted with OPM-2 tumors and PET/CT images were collected 24 h, 3d, and 7d post-injection. Dosimetry data was collected from male and female mice and calculated using OLINDA. Three productions of [Zr]Zr-DFO-Isatuximab were produced using GMP techniques and validated for use in the clinic. RESULTS: Upregulation of CD38 was observed in vitro in CD38 + cells when treated with either pomalidomide or ricolinostat. In vivo evaluation of [Zr]Zr-DFO-Isatuximab showed high selectivity in OPM-2 xenografts. Blocking with an excess of unlabeled Isatuximab reduced the tumor accumulation of [Zr]Zr-DFO-Isatuximab by 45.5-48.5% confirming the in vivo specificity of this radiotracer. Dosimetry calculations were performed and showed an estimated effective dose of 0.359 mSv/MBq in females and 0.327 mSv/MBq in males. Three clinical grade [Zr]Zr-DFO-Isatuximab doses using good manufacturing practices were synthesized which passed all quality control requirements and were stable up to 6 h, thus validating this compound for use in future clinical trials. CONCLUSION: [Zr]Zr-DFO-Isatuximab showed high specificity to CD38 positive cells, had estimated effective doses comparable to other clinically relevant Zr-labeled antibodies, and can be prepared using GMP practices for clinical use.
Molecular Insights into BZW1 Expression and [F]FDG PET/CT Metabolic Parameters in LUAD.
Li J, Wang S, Chen G … +10 more , Hu Y, Wang H, Wei H, Liu H, Cui C, Li Y, Li X, Wang X, Cao J, Wu Z
Mol Imaging Biol · 2026 Feb · PMID 41350974 · Publisher ↗
PURPOSE: Early detection and intervention in lung adenocarcinoma (LUAD) are critical for improving patient prognosis. This study explores the role of basic leucine zipper and W2 domains 1 (BZW1, BZAP45) in regulating mal...
PURPOSE: Early detection and intervention in lung adenocarcinoma (LUAD) are critical for improving patient prognosis. This study explores the role of basic leucine zipper and W2 domains 1 (BZW1, BZAP45) in regulating malignant cellular behavior and glycolytic metabolism in LUAD. PROCEDURES: Bioinformatics and clinical information analysis was conducted to study BZW1 expression and its relationship with prognosis, glycolysis-related genes expression and PET/CT parameters of 2-deoxy-2-[⁸F]fluoro-D-glucose ([F]FDG) in LUAD. BZW1 was knocked out in A549 cell line and verified. In vitro and in vivo studies were performed to analyze BZW1's impact on malignant behaviors and glycolysis. Non-targeted mass spectrometry analyzed xenograft tumor metabolites and potential biomarkers. RESULTS: Bioinformatic analyses identified BZW1 as a pivotal gene driving LUAD progression. The retrospective analysis revealed that BZW1 expression is elevated in LUAD tissues and is significantly correlated with clinical tumor parameters and metabolic parameters obtained from [F]FDG PET/CT. In vitro assays demonstrated that BZW1 overexpression promotes LUAD cell proliferation, migration, and invasion. In vivo experiments with mouse xenograft models confirmed that BZW1 promotes tumor growth. Further analysis revealed that BZW1 may facilitate glycolysis and the Warburg effect by upregulating hypoxia inducible factor-1α (HIF-1α) and cellular Myelocytomatosis (c-Myc). CONCLUSIONS: These findings highlighted the role of BZW1 in LUAD metabolism and may promote tumor progression through modulating of glycolytic pathways. In conclusion, BZW1 is significantly associated with LUAD malignancy and [F]FDG PET/CT derived metabolic parameters. It could provide a potential molecular target for the diagnosis and treatment of LUAD, offering new insights into precision oncology.
Comparison of [Ga]Ga-FAPI-04 PET/CT, [F]FDG PET/CT, Enterography, and Intestinal Ultrasound in Assessing Crohn's Disease.
Zheng J, Zhu H, Zhang L … +4 more , Xu F, Wang C, Wu Z, Miao W
Mol Imaging Biol · 2026 Feb · PMID 41350973 · Publisher ↗
PURPOSE: We aimed to compare the diagnostic performance of [Ga]Ga-FAPI-04 PET/CT, [F]F-FDG PET/CT, enterography and intestinal ultrasound (IUS) in detecting inflamed segments in patients with Crohn's disease (CD), as wel...
PURPOSE: We aimed to compare the diagnostic performance of [Ga]Ga-FAPI-04 PET/CT, [F]F-FDG PET/CT, enterography and intestinal ultrasound (IUS) in detecting inflamed segments in patients with Crohn's disease (CD), as well as in identifying CD-related complications. METHODS: This prospective study enrolled 16 patients with CD. Each patient underwent [Ga]Ga-FAPI-04 PET/CT, [F]F-FDG PET/CT, enterography, and IUS within 14 days. Using endoscopic results as the reference standard, we assessed the diagnostic accuracy and agreement across these imaging modalities for detecting segmental lesions in the proximal upper gastrointestinal (GI) tract and ileocolon. Their performance in identifying CD-associated complications and mesenteric changes was also evaluated. RESULTS: [Ga]Ga-FAPI-04 PET/CT exhibited high sensitivity (73.3%, 95% CI: 0.610-0.829), specificity (97.8%, 95% CI: 0.887-0.996) and accuracy (84.0%, 95% CI: 0.758-0.897) for detecting segmental lesions in the terminal ileum and colon. These performance metrics were comparable to those of enterography, [F]F-FDG PET/CT and IUS (all P > 0.05), with nearly perfect diagnostic agreement observed among these imaging modalities (all κ > 0.81; all P < 0.001). In the upper GI tract and proximal small intestine, its sensitivity (53.8%, 95% CI:0.291-0.768), specificity (92.1%, 95% CI:0.792-0.973) and accuracy (82.4%, 95% CI:0.697-0.904) were similar to [F]F-FDG PET/CT and enterography, with good diagnostic agreement (both κ = 0.73; P < 0.001). However, its resolution was suboptimal for detecting mild lesions. Notably, [Ga]Ga-FAPI-04 PET/CT outperformed other imaging methods in detection rate and sensitivity for identifying CD-associated complications and mesenteric changes. CONCLUSION: [Ga]Ga-FAPI-04 PET/CT may sever as a one-step, non-invasive diagnostic option for CD patients.
Molecular Imaging of Pancreatic Duct Adenocarcinoma Using [F]JR-1004, a Cannabinoid Type 2 Receptor Targeted Positron Emission Tomography (PET) Probe.
Jin C, Cao X, Chen J … +2 more , Mao D, He Q
Mol Imaging Biol · 2026 Feb · PMID 41350972 · Publisher ↗
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a 5-year survival rate below 10% and poor prognosis. Early diagnosis of PDAC remains a significant challenge due to its nons...
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a 5-year survival rate below 10% and poor prognosis. Early diagnosis of PDAC remains a significant challenge due to its nonspecific symptomatology, insufficient reliable biomarkers, aggressive tumor progression with early metastatic spread, and limited effective screening protocols. Recent research indicates cannabinoid type 2 receptor (CB2R) overexpression in PDAC, leading to the development of [F]JR-1004 as a potential CB2R-targeted PET probe to address diagnostic challenges in this aggressive malignancy. PROCEDURES: The probe development utilized computer-aided drug design, incorporating modifications to a triaryl sulfonamide CB2R inverse agonist lead compound. Essential pharmacophoric elements (central sulfonamide, flanking aromatic rings) were preserved, while the para-methoxy group underwent conversion to a tosylate precursor for radiolabeling. Radiolabeling with F was performed using a JiRui OnePlatform 3.1 s synthesizer (synthesis time: 70 min). RESULTS: The radiochemical purity and yield achieved values exceeding 95% and 16.7%, respectively. In vitro studies confirmed [⁸F]JR-1004's specific binding affinity in CB2R-overexpressing cells, with uptake significantly reduced by a CB2R antagonist administration. PET imaging in PDAC mouse models revealed significant accumulation in tumor regions, with receptor specificity validated through CB2R blocking studies. Biodistribution analysis revealed primary probe metabolism through the hepatobiliary system, with maximal uptake in the liver and pancreas. The probe's targeting profile demonstrates notable improvements for PDAC detection compared to the relatively nonspecific uptake patterns of [F]FDG PET in pancreatic imaging. CONCLUSIONS: This investigation presents an innovative molecular imaging approach for early PDAC diagnosis, exhibiting considerable potential for clinical implementation.
Staging Prostate Cancer with AI: A Comparative Study of Large Language Models and Expert Interpretation on PSMA PET-CT Reports.
Ismayilov R, Aktas A, Gencoglu EA … +3 more , Oguz A, Altundag O, Akcali Z
Mol Imaging Biol · 2026 Feb · PMID 41350971 · Publisher ↗
PURPOSE: Accurate staging of prostate cancer is essential for therapeutic decision-making. While PSMA PET-CT reports offer rich clinical data, their unstructured format hinders large-scale analysis. Recent advances in la...
PURPOSE: Accurate staging of prostate cancer is essential for therapeutic decision-making. While PSMA PET-CT reports offer rich clinical data, their unstructured format hinders large-scale analysis. Recent advances in large language models (LLMs) offer new opportunities to extract structured information from narrative radiology reports. However, their ability to perform multi-step clinical reasoning, particularly for cancer staging, remains underexplored. METHODS: In this feasibility study, 80 anonymized, Turkish-language PSMA PET-CT reports were independently interpreted by two LLMs-Gemini 2.5 Pro (Google) and ChatGPT 4o (OpenAI). Using a structured prompt containing an embedded knowledge base (AJCC/CHAARTED criteria) and few-shot examples, both LLMs generated classifications for T, N, M, and overall clinical stage/disease volume. Outputs were benchmarked against expert classifications by a senior nuclear medicine specialist. Performance was evaluated using accuracy, precision, recall, F1-score, and Cohen's kappa. RESULTS: For the composite task of classifying clinical stage and disease volume, Gemini 2.5 Pro achieved an accuracy of 93.8% (95% CI: 86.0-97.9) and a Cohen's kappa of 0.910 (95% CI: 0.834-0.986), while ChatGPT 4o achieved 91.3% accuracy (95% CI: 82.8-96.4) with a kappa of 0.874 (95% CI: 0.786-0.962). For T staging, Gemini showed a higher accuracy point estimate (95.0% [95% CI: 87.7-98.6] vs. 91.3% [95% CI: 82.8-96.4]), while both models excelled at the binary N and M classifications, achieving accuracies above 95% and kappa values indicating near-perfect agreement (κ > 0.900). CONCLUSIONS: LLMs, when guided by expert-informed prompt engineering, can accurately stage prostate cancer from free-text PSMA PET-CT reports and may serve as a powerful assistive tool for data automation, research acceleration, and quality assurance.
Sarcopenia in Aging: Pathogenesis, Diagnosis, and Emerging Therapeutic Frontiers.
Jeyaraman M, Jeyaraman N, Nallakumarasamy A … +7 more , Ramasubramanian S, Muthu S, Murugan S, Rajendran SNS, Rajendran RL, Ahn BC, Gangadaran P
Mol Imaging Biol · 2026 Feb · PMID 41296190 · Publisher ↗
Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, remains a formidable challenge in aging populations. This review synthesizes current knowledge on its multifactorial pathogenesis, i...
Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, remains a formidable challenge in aging populations. This review synthesizes current knowledge on its multifactorial pathogenesis, including mitochondrial dysfunction, oxidative stress, chronic inflammation, apoptosis, and satellite cell impairment. Neuromuscular alterations such as motor unit Remodeling and neuromuscular junction degeneration further exacerbate functional decline. Diagnostic approaches, ranging from DXA, CT, MRI, and ultrasound imaging to functional assessments like handgrip strength and gait speed, exhibit variability that complicates standardization. Therapeutic strategies are equally versatile. Resistance-based exercise and targeted nutritional support remain first-line, but late-phase trials of myostatin-neutralising antibodies (e.g., LY2495655, bimagrumab) and oral selective androgen-receptor modulators (SARMs; e.g., enobosarm, GSK2881078) now show dose-dependent gains in appendicular lean mass and preliminary functional benefits, signalling that combination regimens integrating lifestyle and drug therapy are imminent. Integration of these approaches with personalized medicine paradigms and AI-driven diagnostic tools holds promise for improved outcomes. This review also outlines critical research areas including mechanistic studies, diagnostic standardization, and translational gaps between preclinical models and clinical application. Addressing these challenges requires an interdisciplinary strategy that encompasses molecular, clinical, and public health perspectives to mitigate the personal and societal impacts of sarcopenia. Future efforts must focus on harmonizing diagnostic criteria, refining therapeutic regimens, and leveraging emerging technologies to develop targeted interventions that preserve muscle function and enhance quality of life in the aging population.
A Claudin-1 Near-Infrared Fluorescent Antibody Conjugate for In Vivo Primary and Metastatic Colorectal Cancer Detection.
Primeaux M, Gupta R, Fatima I … +5 more , Talib S, Singh AB, Mohs AM, Bouvet M, Dhawan P
Mol Imaging Biol · 2026 Feb · PMID 41296189 · Publisher ↗
PURPOSE: Despite advancements in colorectal cancer (CRC) therapy, surgery remains the only curative option. Incomplete resection resulting in tumor cell positive surgical margins occurs in ~ 7% of CRC surgeries and is as...
PURPOSE: Despite advancements in colorectal cancer (CRC) therapy, surgery remains the only curative option. Incomplete resection resulting in tumor cell positive surgical margins occurs in ~ 7% of CRC surgeries and is associated with recurrence and poor prognosis. Fluorescence-guided surgery (FGS) enhances tumor detection and enables real-time identification of tumor margins. Claudins, a large family of tight junction proteins, are being explored as cancer biomarkers and therapeutic targets due to their presence on the cell surface, tissue-specific expression, and selective upregulation in carcinomas. Claudin-1 (CLDN1) is overexpressed in CRC and associated with therapy resistance and metastasis, making it a promising target for fluorescence-based tumor detection. PROCEDURES: CLDN1 expression in CRC was analyzed using the Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA-COAD) dataset. To enable in vivo tumor detection, a CLDN1 monoclonal antibody was conjugated to a near-infrared fluorescent dye (CLDN1-IR800). Sensitivity, specificity, and tumor-to-background ratio were tested in vitro and in vivo using CRC cell lines, patient-derived organoids, and an orthotopic, syngeneic model of CRC metastasis. RESULTS: This study demonstrates that CLDN1 is upregulated in 100% of CRC tumors compared to patient-matched normal adjacent colon in the TCGA-COAD dataset, with an average 40-fold increase in expression. CLDN1-IR800 showed specific binding and strong fluorescence in CLDN1-expressing CRC cells, with minimal signal in non-expressing cells or IgG-IR800 controls. In vivo, CLDN1-IR800 produced a significantly higher tumor-to-background ratio in CLDN1-expressing CRC cell line and patient-derived organoid xenografts compared to CLDN1-negative tumors or IgG-IR800-injected mice. Necropsy revealed significantly higher fluorescence in tumors than in other organs. In an orthotopic syngeneic mouse model, both primary and metastatic lesions were detectable. Ex vivo imaging confirmed signal in a panel of patient-derived organoids. CONCLUSIONS: These findings demonstrate CLDN1's potential as a target for tumor detection and FGS in CRC.
First-in-Human Biodistribution and Dosimetry of [C]Trimethoprim.
Young AJ, Doot RK, Cho JK … +11 more , Pham JM, Ordonez AA, Del Castillo AF, Dominguez TL, Dugyala S, Schubert EK, Lee H, Pantel AR, Mach RH, Mankoff DA, Sellmyer MA
Mol Imaging Biol · 2026 Feb · PMID 41275068 · Full text
UNLABELLED: Trimethoprim (TMP) is a reversible inhibitor of the prokaryotic enzyme dihydrofolate reductase (DHFR) used for the treatment or prophylaxis of bacterial infections. [C]trimethoprim ([C]TMP) is a positron emis...
UNLABELLED: Trimethoprim (TMP) is a reversible inhibitor of the prokaryotic enzyme dihydrofolate reductase (DHFR) used for the treatment or prophylaxis of bacterial infections. [C]trimethoprim ([C]TMP) is a positron emission tomography (PET) imaging isotopologue of TMP. TMP binds with 30,000-fold greater affinity to bacterial DHFR over the homologous mammalian enzyme in vitro, suggesting [C]TMP may selectively accumulate in tissues with cells expressing bacterial DHFR. This study characterizes the biodistribution and dosimetry of [C]TMP, informing its use in imaging bacterial infections and tracking mammalian cells expressing eDHFR as a reporter gene. METHODS: Four males with suspected infection, aged 59 ± 10 years old (mean ± SD) received 3 serial PET/CT scans after injection of 346 ± 305 MBq (range 129-797 MBq) of [C]TMP. Organ activities were measured in MIM v6.7, including brain, kidneys, spleen, liver, heart, lungs, bladder, intestines, gallbladder, pancreas, thyroid, and red marrow. Dosimetry calculations were performed in Olinda | EXM v1.1. Additionally, a dynamic whole-body PET/CT scan was performed on a separate participant. The associated trial was registered as NCT03424525. RESULTS: [C]TMP injections were well tolerated with no adverse events. The average injected activity of 346 MBq of [C]TMP yielded an estimated average dose of 4.9 mSv in the highest uptake organ (liver), 4.1 mSv in the spleen, and an effective dose of 1.6 mSv. Suspected sites of infection displayed uptake above background. CONCLUSION: [C]TMP PET was safe and demonstrated low background uptake in most tissues. The data suggests feasibility for evaluation of varied bacterial infections, including musculoskeletal infections. Absorbed doses allow multiple [C]TMP PET scans each year within Radioactive Drug Research Committee (RDRC) limits, potentially enabling monitoring of infections and treatment response.
In-Ovo Imaging with Ostrich Eggs: Eggshell Attenuation in CT and Limitations of Organ Dosimetry.
Kühnel C, Schmidt TN, Perkas O … +4 more , Pomraenke M, Greiser J, Freesmeyer M, Winkens T
Mol Imaging Biol · 2025 Dec · PMID 41252067 · Full text
Ostrich eggs have recently attracted interest as an alternative model in preclinical nuclear medicine imaging. The ability to be used in clinical PET/CT (positron emission tomography/computed tomography) systems and thei...
Ostrich eggs have recently attracted interest as an alternative model in preclinical nuclear medicine imaging. The ability to be used in clinical PET/CT (positron emission tomography/computed tomography) systems and their ethical profile are advantageous over conventional rodent models and other avian systems. Nevertheless, concerns regarding radiation exposure during repeated CT (computed tomography) imaging of developing embryos remain inadequately addressed. This study aimed to characterize the attenuation impact of eggshells in ostrich eggs and to evaluate the potential for organ-specific dose assessment. A representative ostrich egg was selected from a cohort of 168 eggs and used to construct a dimensionally matched 3D-printed phantom. Organ weights of 83 embryos were documented on development day (DD) 37 to provide a basis for future organ-level dosimetric modeling. Thermoluminescence dosimeters (TLDs) were positioned along the z-axis within both the egg and phantom, and CT dose distributions were measured using a clinical PET/CT system. The mean absorbed dose in the real egg was 16.3 ± 2.0% lower than in the phantom, attributable to radiation attenuation by the 1.89 ± 0.12 mm thick eggshell. CTDI (computed tomography dose index) values remained stable across developmental stages (DD 0-37). Our findings confirm that the ostrich eggshell exerts a significant shielding effect during CT imaging. While ostrich eggs are suitable for serial in-ovo imaging, embryo positioning remains a major limitation for precise dosimetry. Organ weight data enable potential use of AI (artificial intelligence)-based modeling to improve spatial dosimetry accuracy. This study provides essential groundwork for dose optimization and radioprotection in preclinical imaging protocols using ostrich eggs.
Nanophotonics in Molecular Imaging and Biomedicine: Diagnostics, Therapies, and Translational Challenges.
Hassan YM, Wanas A, Ali AA … +1 more , El-Sayed WM
Mol Imaging Biol · 2025 Dec · PMID 41249751 · Full text
Nanophotonics-the manipulation of light at the nanometer scale within biological systems-is transforming molecular imaging and photobiology, enabling advanced in vivo imaging, diagnostics, and therapy guidance. This revi...
Nanophotonics-the manipulation of light at the nanometer scale within biological systems-is transforming molecular imaging and photobiology, enabling advanced in vivo imaging, diagnostics, and therapy guidance. This review outlines core nanophotonic principles, including surface plasmon resonance, optical confinement, and photon-matter interactions, underpinning emerging molecular imaging probes and diagnostic tools. Biocompatible nanomaterials such as quantum dots, gold nanoparticles, and photonic metamaterials enable highly sensitive, selective imaging and biosensing for early, minimally invasive disease detection and monitoring. Targeted photothermal and photodynamic therapies using near-infrared (NIR) and NIR-II light advance image-guided interventions, allowing deeper tissue penetration with minimal collateral damage. We also discuss the integration of nanophotonic components into lab-on-a-chip and microfluidic platforms for point-of-care diagnostics, accelerating clinical translation. Additionally, machine learning enhances molecular imaging analysis and probe optimization, enabling real-time data interpretation and predictive modeling tailored to patient-specific profiles. This article is a narrative review that emphasizes recent advancements from 2021-2025, identified through targeted database searches, highlighting progress, research gaps, and future perspectives for disease-specific applications. While these advances hold promise, challenges remain in biocompatibility, light penetration, scalability, and regulatory approval. Collectively, integrating nanophotonics with molecular imaging, machine learning, and personalized medicine frameworks marks a step toward next-generation precision diagnostics and image-guided therapeutics.
Feasibility of Early Dynamic F-FDG PET/CT Imaging for Predicting EGFR and TP53 Mutations in Lung Adenocarcinoma.
Zhang Y, Liu G, Guan Y … +2 more , Li B, Zhang Y
Mol Imaging Biol · 2025 Dec · PMID 41239154 · Publisher ↗
OBJECTIVE: To investigate the feasibility of early dynamic 2-[F]-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging in predicting epidermal growth factor receptor (EGFR) an...
OBJECTIVE: To investigate the feasibility of early dynamic 2-[F]-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging in predicting epidermal growth factor receptor (EGFR) and tumor protein 53 (TP53) mutation status in lung adenocarcinoma (AC). METHODS: In total, 81 patients with lung nodules underwent early dynamic PET (10 min after injection) and late static PET (60 min after injection), and 41 (18 male, 23 female; mean age 64 ± 10 years) with confirmed AC were included in the final analysis. Dynamic images were reconstructed into 25 frames, and time-to-activity curves were generated. An irreversible two-tissue compartment model was used to derive kinetic parameters (K k, k, Ki, and MR). EGFR and TP53 mutation statuses were determined via histological analysis. Statistical tests, including the Wilcoxon rank-sum test, Kruskal-Wallis H test, and Spearman's correlation, were used to assess differences and associations among groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance. RESULTS: In patients with AC, k, Ki, and MR were strongly correlated with SUV (r = 0.821, 0.862, and 0.778, respectively; all P < 0.001). SUV, k, Ki, and MR differed significantly between patients with AC and SCC, as well as across TNM and pathological stage subgroups (P < 0.05). SUV and k were significantly lower in the EGFR-positive group, while Ki was higher in the TP53-positive group (P < 0.05). AUCs for predicting EGFR mutation were 0.718 (SUV) and 0.776 (k), and 0.703 (Ki) for TP53 mutation. CONCLUSIONS: Early dynamic F-FDG PET/CT may serve as a valuable non-invasive tool for predicting EGFR and TP53 mutation status in AC, for screening patients for targeted therapy.
Validation of Lung [F]FDG Uptake as a Quantitative PET Biomarker for Influenza-Associated Pulmonary Inflammation.
Victorio CBL, Gupta S, Ganasarajah A … +2 more , Ong J, Chacko AM
Mol Imaging Biol · 2025 Dec · PMID 41193777 · Full text
PURPOSE: Influenza (flu) is a respiratory illness caused by lung infection with influenza viruses. This study establishes lung [F]FDG uptake by PET/CT as an accurate measure of lung inflammation associated with influenza...
PURPOSE: Influenza (flu) is a respiratory illness caused by lung infection with influenza viruses. This study establishes lung [F]FDG uptake by PET/CT as an accurate measure of lung inflammation associated with influenza A virus (IAV) H1N1 infection. PROCEDURES: Immunocompetent BALB/c mice were infected with a highly lethal dose of influenza A virus (PR8 strain) and intravenously injected with [F]FDG. Ex vivo tissue biodistribution was assessed by gamma counting, while in vivo tissue biodistribution was analyzed by VOI analysis of PET/CT images. Disease severity was also investigated by VOI measurements of high-resolution lung CT images. Infection and inflammation were confirmed by immunohistochemical staining; while viral replication and expression of inflammatory proteins (cytokines and chemokines) were measured in lung tissues by qRT-PCR and multiplex ELISA, respectively. RESULTS: Ex vivo tissue biodistribution of [F]FDG revealed that the lungs were the only relevant imaging target in influenza-infected mice. Lung [F]FDG uptake on PET/CT images increased with disease severity and exhibited 1.53-fold increase on day 1 and up to 2.63-fold increase on day 6 post-infection compared to pre-infection levels. Lung uptake correlated with the increased production of pro-inflammatory proteins associated with influenza infection. CONCLUSIONS: Lung [F]FDG uptake on PET images is a non-invasive molecular biomarker of influenza-A virus-induced lung inflammation and disease, effectively distinguishing infected from non-infected lungs as early as day 1 post-infection.
A Guide to Ex Vivo Biodistribution Studies with Radiotracers in Rodent Models.
Imlimthan S, Berton C, Poty S … +2 more , Holland JP, Sarparanta M
Mol Imaging Biol · 2025 Dec · PMID 41152646 · Full text
Preclinical biodistribution studies are required at an early stage of radiopharmaceutical development to determine tracer pharmacokinetics in clinically relevant animal models of human diseases. When combined with quanti...
Preclinical biodistribution studies are required at an early stage of radiopharmaceutical development to determine tracer pharmacokinetics in clinically relevant animal models of human diseases. When combined with quantitative analysis from non-invasive imaging, biodistribution experiments provide essential data on the uptake, retention, binding specificity, metabolism, and clearance of radiotracers in both target and non-target tissues. Most research groups have developed in-house protocols to perform these studies in a reproducible manner. However, there is a general lack of consistency in how different groups carry out biodistribution experiments. In addition to practical differences that occur during tissue collection (for example, washing and blotting dry the tissue, perfusion, sampling site for a given tissue, etc.), other aspects of biodistribution experiments, which often vary include the methods used for calibrating the injected activity, the processes used to calculate mass normalized tissue uptake (i.e. percentage of injected dose per gram [%ID g] or percentage of injected activity per gram of tissue [%IA g]) values, differences in data processing and statistical analyses (particularly error propagations and calculation of tissue contrast ratios), and variations in how the methods and data are reported and interpreted. This variability hinders the direct comparison of datasets produced at different laboratories. Here, we present a comprehensive guideline for conducting ex vivo biodistribution experiments with radiotracers in rodent models. An open source, freely accessible online biodistribution calculator and associated spreadsheet are provided which can be employed to compute the percent of injected dose per gram of tissue (%ID g), standardized uptake value (SUV by mass), and target-to-background tissue contrast ratios. Finally, advice concerning biodistribution data presentation and statistical analysis are given to help the reader harness the full power of ex vivo biodistribution studies in radiotracer development.
Comparative Study of [F]DPA714 and [F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis.
Stammes MA, Vierboom MPM, Sombroek CC … +9 more , Bakker J, Meijer L, Vervenne RAW, Hofman SO, Nutma E, Kondova I, Windhorst AD, Langermans JAM, Verreck FAW
Mol Imaging Biol · 2025 Dec · PMID 41120776 · Full text
PURPOSE: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tubercul...
PURPOSE: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages. PROCEDURES: We compared two tracers: [F]DPA714 to the widely applied marker [F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers. RESULTS & CONCLUSIONS: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [F]FDG progressively increased in line with the developing TB pathology, while [F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.
[F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy.
Antons MJ, Kloiber-Langhorst S, Hirner-Eppeneder H … +12 more , Schaefer R, Stueckl J, Palumbo G, Oos R, Herr FL, Lindner S, Ziegler S, Brendel M, Ricke J, Werner RA, Heimer MM, Cyran CC
Mol Imaging Biol · 2025 Dec · PMID 41102571 · Publisher ↗
PURPOSE: Immune checkpoint inhibition has shown promising results in malignant melanoma, but not all patients respond equally well, necessitating early, accurate monitoring of immunotherapy response. [F]FDG-PET/CT aids i...
PURPOSE: Immune checkpoint inhibition has shown promising results in malignant melanoma, but not all patients respond equally well, necessitating early, accurate monitoring of immunotherapy response. [F]FDG-PET/CT aids in characterising therapy response beyond morphology, but validated imaging biomarkers for immunotherapy response remain scarce. This study investigated three-time point [F]FDG-PET/CT to monitor combined anti-PD-L1/anti-CTLA-4 immunotherapy in murine melanoma allografts and compared quantitative in vivo imaging biomarkers with ex vivo biomarkers from multiparametric immunohistochemistry at each time point. PROCEDURES: Melanoma cells (B16-F10) were injected subcutaneously into C57BL/6 mice (n = 40). Seven days post-inoculation, baseline [F]FDG-PET/CT was conducted. Animals were randomized into two groups; the therapy group received 5 i.p.-injections of anti-PD-L1/anti-CTLA-4 (20 µg/kg) on days 7, 9, 11, 13 and 15 after tumor cell inoculation. The control group received sham treatment. PET/CT was performed at baseline (day 7 post inoculation), follow-up 1(day 13; FU-1) and follow-up 2 (day 19; FU-2). Tumor allografts were harvested at each time point for immunohistochemistry (CD8, Ki-67, TUNEL) to validate imaging parameters (MTV, SUVmax). RESULTS: At FU-1, the therapy group exhibited significantly lower MTV than the control group (p = 0.004). At FU-2, MTV and SUVmax were significantly lower (MTV: p = 0.008; SUVmax: p = 0.0003) compared to controls. Ex vivo analysis revealed significant anti-tumor effects in the therapy group, with higher apoptosis rates (FU-1: p = 0.012; FU-2: p = 0.001), more CD8-positive T-cells (FU-2: p = 0.003) and lower tumor cell proliferation (FU-1: p = 0.012; FU-2: p = 0.012). CONCLUSIONS: Multi-time point [F]FDG-PET/CT allowed for early non-invasive monitoring of combined anti-PD-L1/anti-CTLA-4 immunotherapy in experimental melanomas, validated by multiparametric immunohistochemistry with significant pro-immunogenic, pro-apoptotic and anti-proliferative effects.
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