Mol Imaging Biol [JOURNAL]
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200 papers
Epithelial Cell Adhesion Molecule Is an Accurate Target for Fluorescence Guided Imaging of Lymph Nodes.
McGovern KA, Welch KO, Krouse R … +9 more , Brown M, Chen L, Guo K, Huang J, Mlakar J, Delikatny EJ, Gruev V, Zhang P, Singhal S
Mol Imaging Biol · 2025 Dec · PMID 41087662 · Full text
PURPOSE: Lymph node (LN) excision is critical in oncologic surgery to provide important therapeutic and diagnostic information. LN evaluation helps in staging cancers, predicting prognosis and improving survival. The ult...
PURPOSE: Lymph node (LN) excision is critical in oncologic surgery to provide important therapeutic and diagnostic information. LN evaluation helps in staging cancers, predicting prognosis and improving survival. The ultimate wish of a surgical oncologist would be to localize and dissect all pathologically positive LNs while avoiding the morbidity of removing true negative LNs. The goal of our study was to identify a reliable marker for intraoperative molecular imaging of LNs with cancer cells from non-small cell lung cancer versus a LN without. PROCEDURES: We identified Epithelial Cell Adhesion Molecule (EpCAM), a membrane protein normally expressed in epithelial tissues including lung. We performed immunofluorescence staining on human specimens with a conjugated anti-EpCAM monoclonal antibody. RESULTS: Fluorescence was significantly higher in LNs with metastases as shown in 48 positive LNs from patients with resected primary lung cancer. There was high fluorescence in both hilar and mediastinal LNs, and in all primary tumor histologies. CONCLUSIONS: EpCAM may be useful for the surgical oncologist for intraoperative molecular imaging of positive LNs from lung cancer.
Detection of Prostate Cancer Metastases During Pelvic Lymph Node Dissection with the PSMA-Targeted Fluorescent Agent OTL78: A Phase II Study.
Stibbe JA, Linders DFG, Faber RA … +7 more , Bevers RFM, van Gennep EJ, Crobach SASLP, Bhairosingh SS, Biro TG, Burggraaf PJ, Vahrmeijer PAL
Mol Imaging Biol · 2025 Dec · PMID 41068509 · Full text
PURPOSE: This study aimed to assess the feasibility of intraoperative fluorescence imaging using the PSMA-targeted fluorescent tracer OTL78 for detecting lymph node metastases during pelvic lymph node dissection (PLND) i...
PURPOSE: This study aimed to assess the feasibility of intraoperative fluorescence imaging using the PSMA-targeted fluorescent tracer OTL78 for detecting lymph node metastases during pelvic lymph node dissection (PLND) in patients undergoing staging or salvage surgery for prostate cancer. PROCEDURES: In a prospective pilot study, six patients scheduled for robot-assisted PLND received a single intravenous infusion of OTL78 at a dose of either 0.06 mg/kg or 0.03 mg/kg, administered 1-2 h prior to surgery. Intraoperatively, lymph node clusters were evaluated using fluorescence imaging. Post-surgical histopathological analysis and immunohistochemistry were performed to confirm tumor presence and PSMA overexpression in fluorescent nodes. The primary outcome was the feasibility of fluorescence imaging in detecting metastatic lymph nodes during PLND. RESULTS: Fluorescence imaging demonstrated a sensitivity of 66.7% and specificity of 91.7% for identifying metastatic lymph nodes. The positive predictive value was 66.7%, and the negative predictive value was 91.7%. Metastasized lymph nodes (MLN) exhibited significantly higher median fluorescence intensity (MFI) than benign lymph nodes (BLN): 0.51 [IQR 0.11-0.74] vs. 0.06 [IQR 0.03-0.12], p = 0.024. Immunohistochemistry confirmed PSMA overexpression in fluorescent malignant regions. No adverse reactions to the tracer were reported. CONCLUSIONS: Intraoperative fluorescence imaging with the tracer OTL78 is a feasible technique for identifying metastatic lymph nodes during PLND. Fluorescence guidance may assist in detecting small metastatic deposits within nodal clusters that are otherwise difficult to localize. Larger studies are needed to validate these findings and optimize the imaging protocol for broader clinical use.
Metabolic Shift Mirrors GBM Immunity to Anti-PD-L1 Immunotherapy: A Deuterium MRS Study.
Garbow JR, Ge X, Johanns TM … +3 more , Engelbach JA, Rich KM, Ackerman JJH
Mol Imaging Biol · 2025 Dec · PMID 41044469 · Full text
BACKGROUND/OBJECTIVES: Immune checkpoint blockade (ICB) therapy has been ineffective in glioblastoma (GBM) that recurs following standard-of-care resection and chemoradiation of the primary tumor. Herein, we investigate...
BACKGROUND/OBJECTIVES: Immune checkpoint blockade (ICB) therapy has been ineffective in glioblastoma (GBM) that recurs following standard-of-care resection and chemoradiation of the primary tumor. Herein, we investigate whether the delayed effect of intracranial radiation alters the tumor lesion metabolic profile. METHODS: Naïve (non-irradiated) GL261 tumor cells were implanted into the brains of C57BL/6 mice. Brains of one cohort were hemispherically irradiated six weeks prior to implantation, ultimately resulting in ICB refractory GBM. Brains of the control cohort were not irradiated. Following subcutaneous infusion of [6,6-H] glucose (Glc), single voxel deuterium metabolic imaging (DMI) monitored Glc uptake and the production of semi-heavy water (HOD), H-lactate (Lac) and the 50/50 mix of [H-glutamate + H-glutamine] (Glx). RESULTS: GL261 tumors growing in previously irradiated brain showed reduced Warburg effect (aerobic glycolysis; glucose → lactate) and greater TCA cycle activity (respiration, oxidative phosphorylation) relative to tumors growing in non-irradiated brain as evidenced by cohort differences in the ratios Glx/Lac (p < 0.01), Glx/Glc (p < 0.02), and Lac/Glc (p < 0.01). CONCLUSIONS: A metabolic program skewed toward oxidative phosphorylation and away from glycolysis has been associated with immune dysfunction. This study documents such a skewed metabolic state in ICB refractory GL261 GBM growing in irradiated brain (tumors were not irradiated) compared to control brain.
Peptide Receptor Radionuclide Therapy with Lu-177-DOTATATE and Monitoring with Somatostatin Receptor PET/CT in Patients with Advanced Differentiated Thyroid Carcinoma.
Kunte SC, Wenter VU, Holzgreve A … +9 more , Sheikh GT, Widjaja L, Gildehaus FJ, Lindner S, Schirrmacher R, Spitzweg C, Auernhammer CJ, Werner RA, Zacherl MJ
Mol Imaging Biol · 2025 Dec · PMID 41023438 · Full text
PURPOSE: Peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE is an established treatment option for neuroendocrine tumors (NETs) and has been extended to other somatostatin receptor (SSTR)-expressing tumors...
PURPOSE: Peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE is an established treatment option for neuroendocrine tumors (NETs) and has been extended to other somatostatin receptor (SSTR)-expressing tumors. We aimed to determine its efficacy and safety profile in patients with advanced radioiodine-refractory differentiated thyroid carcinoma (DTC). METHODS: Seven radioiodine-refractory DTC patients undergoing at least two cycles of PRRT were included. Patients were subdivided into continuous treatment (defined as sequential application of PRRT; 5/7 (71.4%)) vs. discontinuous treatment (with at least one-year PRRT-free interval; 2/7 (28.6%)). Baseline SSTR PET was analyzed to determine patients' eligibility for PRRT. Response was assessed by tumor control as defined by stable (± 30.0%) or decreasing (≥ 30.0%) total tumor volume (PET-derived TTV), thyroglobulin (Tg) and RECIST 1.1 criteria. RESULTS: SSTR PET showed discernible high uptake (maximum standardized uptake values, 10.4 ± 8.6) in metastases, in particular in the skeleton. Continuous PRRT showed variable tumor control (stable disease / response; TTV: 3/5 (60.0%); Tg: 2/5 (40.0%); RECIST 1.1: 3/5 (60.0%)). All patients undergoing discontinuous PRRT exhibited concordant stable disease upon first follow-up and renewed tumor control upon reinitiating PRRT (RECIST 1.1; decreasing TTV and Tg levels). No Common Terminology Criteria for Adverse Events (CTCAE) Grade 3-5 events occured in both groups. CONCLUSION: In advanced radioiodine-refractory DTC, PRRT may be beneficial even after treatment interruptions, without major side effects. Given the small cohort and retrospective design, further prospective studies are needed to optimize PRRT strategies in DTC, in particular in a rechallenge scenario.
Gold Nanoparticles in Atherosclerosis: A Dual Approach to Diagnosis and Therapy.
Mirhadi E, Kesharwani P, Sukhorukov VN … +1 more , Sahebkar A
Mol Imaging Biol · 2025 Dec · PMID 40983820 · Publisher ↗
Atherosclerosis (AS) is a chronic condition defined by the accumulation of plaque fundamentally resulting from the deposition of low-density lipoprotein and fibrous compounds within injured arteries. Current treatments f...
Atherosclerosis (AS) is a chronic condition defined by the accumulation of plaque fundamentally resulting from the deposition of low-density lipoprotein and fibrous compounds within injured arteries. Current treatments for atherosclerosis are effective, but the complex and not fully understood underlying mechanisms limit their effectiveness. Moreover, early detection of AS continues to be a real challenge. Innovative therapeutic approaches, such as the application of nanomedicines and theragnostic, are increasingly attracting the interest of researchers globally. Gold nanoparticles (AuNPs) exhibit significant potential as theragnostic agents in the context of atherosclerosis, providing both diagnostic and therapeutic functionalities. This review will discuss current strategies utilizing AuNPs and explore potential future advancements involving theragnostic AuNPs that may aid in addressing AS.
Preclinical Evaluation of an Anti-EphA2 Minibody-Based ImmunoPET Agent as a Diagnostic Tool For Cancer.
Birikorang PA, Wedaarachchi HEG, Smith JA … +2 more , Kohanbash G, Edwards WB
Mol Imaging Biol · 2025 Dec · PMID 40973914 · Publisher ↗
PURPOSE: In this study, we report the development and characterization of a copper-64 (Cu) radiolabeled anti-EphA2 minibody (Mb) for pre-treatment characterization of antigen expression via Positron Emission Tomography (...
PURPOSE: In this study, we report the development and characterization of a copper-64 (Cu) radiolabeled anti-EphA2 minibody (Mb) for pre-treatment characterization of antigen expression via Positron Emission Tomography (PET). Minibodies, ≈85 kDa molecular weight antibody fragments, are advantageous as targeting molecules due to accelerated serum clearance which enables imaging at earlier time points relative to the parent IgG. As EphA2, a tyrosine kinase receptor, is overexpressed in various cancer types with minimal expression in normal tissue, rapid quantification of EphA2 expression could be beneficial for patient stratification. PROCEDURES: Recombinantly produced anti-EphA2-Mb was evaluated for purity, stability, affinity, and in vivo target localization. Following bifunctional chelator conjugation, radiolabeling with Cu and evaluating purity, stability and immunoreactivity of resultant radioimmunoconjugate, [Cu]Cu-NOTA-anti-EphA2-Mb, 11.1 MBq (300 μCi) and 0.2 MBq (5 μCi) doses were administered to HT1080-fibrosarcoma-bearing nude mice for in-vivo PET imaging and ex-vivo biodistribution analyses respectively at 4 and 24 h post-injection (p.i.). Antigen-specificity was assessed via a blocked control group which received the dose co-administered with non-radiolabeled anti-EphA2-Mb. RESULTS: Anti-EphA2-Mb produced via recombinant protein expression was pure, stable and had high binding affinity to human EphA2 antigen (K = 0.63 ± 0.24 nM). When labeled with Cu via NOTA, [Cu]Cu-NOTA-anti-EphA2-Mb had high purity, in-vitro stability in PBS and mouse serum up to 24 h, and high immunoreactivity. On administering to tumor-bearing mice, [Cu]Cu-NOTA-anti-EphA2-Mb exhibited rapid tumor targeting with 25.53±2.92%ID/g at 4 h, and 22.13±7.68%ID/g at 24 h p.i. Competitive inhibition reduced tumor uptake (11.24±0.88%D/g, 24 h p.i., p = 0.0286). There was minimal uptake of the radiotracer in non-target tissues, except kidney and liver, and fast clearance from the blood, with high tumor to blood ratios. Tumor SUV values obtained from region of interest (ROI) Quantification of the PET images were 1.13±0.03 and 1.08±0.06 at 4 and 24 h respectively. CONCLUSION: Our findings demonstrate that anti-EphA2-Mb is an excellent targeting molecule, and [Cu]Cu-NOTA-anti-EphA2-Mb is a promising immunoPET agent with potential for use for other theranostic applications.
Today's Research, Tomorrow's Practice - White Paper from the Translation of New Therapy (TNT) Radiotheranostics Kick-off Pre-meeting of the Annual World Molecular Imaging Conference 2024.
Krebs S, Baird L, Pirovano G … +6 more , Yamaguchi A, Coll RP, Lee JT, Carroll LS, Pomper MG, Manning HC
Mol Imaging Biol · 2025 Dec · PMID 40971127 · Publisher ↗
Theranostics, a concept combining "therapy" and "diagnostics", is poised to enter an exponential growth phase. By using specific diagnostic markers to guide the selection and application of targeted treatments directed a...
Theranostics, a concept combining "therapy" and "diagnostics", is poised to enter an exponential growth phase. By using specific diagnostic markers to guide the selection and application of targeted treatments directed at those markers, this approach aims to improve effectiveness and reduce unnecessary interventions. While several agents have been approved by the FDA recently, multiple additional theranostics are being developed, studied in clinical trials and expected to enter clinical practice in short order. As part of the "Translation of New Therapy (TNT) Interest Group's Radiotheranostics Kick-off" pre-meeting of the annual World Molecular Imaging Conference (WMIC) 2024 over 350 attendees with 10% leaders from industry, 60% senior and junior investigators in academia and 30% trainees discussed the key challenges and opportunities in implementing a theranostic research program in academia, which are addressed in this white paper. Overarching themes included funding, regulatory hurdles, and workforce training. Panel recommendations included leveraging existing expertise and patient populations, securing revenue streams, exploring alternative funding sources, and developing a multifaceted approach to promote training, education and public awareness, including fostering academic-industry partnerships. By shedding light on the gap between research and real-world program implementation, this white paper and forthcoming pre-meetings at WMIC aim to define a practical framework for building successful programs based on insights from recent research.
Development of New NanoAlbumin-based Radiotracers: Preclinical Evaluation Of [Ga]Ga-DOTA-nanoHSA Conjugates for Lymphatic Imaging Applications.
Kuniyil Kulangara V, Abreu Diaz AM, Elkashef SM … +5 more , Ruiz Pena M, Kiseleva M, Leon Chaviano S, Leung YH, Nandi I
Mol Imaging Biol · 2025 Oct · PMID 40954414 · Publisher ↗
PURPOSE: Sentinel lymph node (SLN) mapping is a critical procedure in the staging and treatment of cancers, such as breast cancer and melanoma. Current radiocolloids used in SLN localization, like [Tc]Tc-Sulfur Colloid,...
PURPOSE: Sentinel lymph node (SLN) mapping is a critical procedure in the staging and treatment of cancers, such as breast cancer and melanoma. Current radiocolloids used in SLN localization, like [Tc]Tc-Sulfur Colloid, face limitations in imaging resolution and specificity. This study aims to evaluate the biodistribution of [Ga]Ga-DOTA-nanoHSA, a novel nanoparticle-based radiotracer, for SLN mapping using PET/CT imaging in both healthy and tumor-bearing murine models and compare results with [Tc]Tc-Sulfur Colloid as the current gold standard for lymph node staging in breast cancer. Additionally, the maximum tolerated dose and potential systemic toxicity of the carrier were assessed in humanized mice. METHODS: Nanoalbumin radiotracers were prepared by thermal denaturation of human serum albumin (HSA), followed by conjugation with 2,2',2″,2″'-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) and labeling with gallium-68. The stability of [Ga]Ga-DOTA-nanoHSA was evaluated in the tracer formulations and in mouse serum. The novel radiotracers were administered subcutaneously and intratumorally in healthy and tumor-bearing mice, respectively, to evaluate SLN uptake via PET/CT imaging. Biodistribution was assessed in major organs, and the tracers' ability to accurately localize SLNs was compared to an existing standard. Toxicity was evaluated in humanized mice, where body weight, clinical scoring, and blood chemistry were monitored over a 14-days period. Mice received escalating doses of DOTA-nanoHSA to determine the maximum tolerated dose. RESULTS: [Ga]Ga-DOTA-nanoHSA tracers (30 nm and 70 nm) were reliably produced with high radiochemical purity (RCP > 90%). The stability of [Ga]Ga-DOTA-nanoHSA (30 nm) in the final formulations at pH 3.5 and 7.0 and in mouse serum was confirmed up to 4-6 h. [Ga]Ga-DOTA-nanoHSA (30 nm) demonstrated effective SLN localization in both healthy and tumor-bearing mice, with high uptake in SLNs and minimal off-target accumulation in non-lymphatic organs. DOTA-nanoHSA was well-tolerated in humanized mice, with no significant changes in body weight, clinical scores, or blood chemistry parameters, even at higher doses. No dose-dependent toxicity was observed. CONCLUSION: [Ga]Ga-DOTA-nanoHSA (30 nm) demonstrated significant potential as a novel imaging agent for SLN mapping. Its favorable toxicity profile, combined with its effectiveness in SLN localization, suggests it could be a valuable alternative for SLN biopsy in clinical practice. Further studies are warranted to confirm these findings in human trials.
Effects of Age and BMI on Histamine H3 Receptor Availability in Healthy Humans.
Yang Y, Ibrahim W, Gravel P … +11 more , Pittman B, Hoye J, Cool R, Sadabad FE, Zheng MQ, Pittenger C, Gallezot JD, Carson RE, Huang H, Radhakrishnan R, Matuskey D
Mol Imaging Biol · 2025 Oct · PMID 40938339 · Publisher ↗
PURPOSE: To assess alterations in H3R availability with age and body mass index (BMI) in healthy humans using in vivo [C]GSK189254 positron emission tomography (PET) imaging. PROCEDURE: Twenty-four healthy individuals (2...
PURPOSE: To assess alterations in H3R availability with age and body mass index (BMI) in healthy humans using in vivo [C]GSK189254 positron emission tomography (PET) imaging. PROCEDURE: Twenty-four healthy individuals (2 females, 22 males; age range 20-47 years) were scanned with [C]GSK189254 with High-Resolution Research Tomograph (HRRT) or HR plus scanner. Regional V (volume of distribution) values were computed using the two-tissue compartment model. The correlation between V and age, BMI were examined, adjusting for relevant potential confounding effects of age or gender and injected mass. RESULTS: H3R availability (V) was correlated with age but not BMI. V displayed a negative correlation with age in the anterior cingulate cortex (r = -0.61, p = 0.004), frontal cortex (r = -0.50, p = 0.020), olfactory cortex (r = -0.50, p = 0.022), parietal cortex (r = -0.58, p = 0.006), cerebellum cortex (r = -0.53, p = 0.013), insula (r = -0.48, p = 0.027), putamen (r = -0.46, p = 0.034), thalamus (r = -0.45, p = 0.038), and hippocampus (r = 0.45, p = 0.039). CONCLUSION: This in vivo H3R study found a significant age-related decline in most cortical and subcortical regions.
PSMA-1-DOTA Potentially for Effective Targeted Radioligand Therapy of Prostate Cancer.
Wang X, Sergeeva O, Sergeev M … +9 more , Zhang L, Lockwood Z, Wojtylak P, Sangster R, Reichert D, Berridge M, Weber W, Lee Z, Basilion JP
Mol Imaging Biol · 2025 Oct · PMID 40897948 · Full text
PURPOSE: While PSMA-targeted radioligand therapy (RLT) has shown remarkable efficacy for treating end-stage prostate cancer, the α-emitting RLT often results in severe salivary gland toxicity, limiting its use. Various s...
PURPOSE: While PSMA-targeted radioligand therapy (RLT) has shown remarkable efficacy for treating end-stage prostate cancer, the α-emitting RLT often results in severe salivary gland toxicity, limiting its use. Various strategies to mitigate this side effect have been attempted with limited success. Accordingly, this study introduced a new PSMA-targeting ligand with more favorable binding characteristics than the existing ligands. PROCEDURES: The binding affinity of PSMA-1-DOTA to PSMA was compared with that of PSMA-11 and PSMA I&T. Comparison of uptake in the salivary glands, kidneys and PC3pip tumor cells in the xenograft mouse models between [ Ga]Ga-PSMA-1-DOTA, [ Ga]Ga-PSMA-11 and [ Ga]Ga-PSMA I&T was conducted with microPET/CT within the same week. The same mouse models were treated with [Lu]Lu-PSMA-1-DOTA or [Lu]Lu-PSMA-617. A compassionate use PET imaging study on a patient with metastatic castration-resistant prostate cancer was performed using [ Ga]Ga-PSMA-1-DOTA. RESULTS: The binding affinity of PSMA-1-DOTA to PSMA was found to be approximately four times greater than other PSMA-targeted ligands. Imaging with microPET/CT revealed significantly lower kidney, uptake and little salivary and lacrimal gland uptake with [ Ga]Ga-PSMA-1-DOTA compared to other PSMA-radioligands. Preclinical efficacy studies demonstrated that [Lu]Lu-PSMA-1-DOTA inhibited tumor growth comparable to that with [Lu]Lu-PSMA-617, suggesting its potential to enhance the therapeutic window of targeted RLT by avoiding damage to the salivary glands. The compassionate use PET imaging confirmed the reduced salivary gland uptake of [ Ga]Ga-PSMA-1-DOTA in the patient, indicating its potential utility as a targeting agent for RLT with α- or β-emitting radionuclides in patients with PSMA-positive prostate cancer. CONCLUSION: PSMA-1-DOTA shows reduced uptake in salivary glands while effectively targeting PSMA-expressing tumors, thus potentially avoiding the side effects of xerostomia, and possibly moving PSMA-targeted RLT to a more frontline therapy for prostate cancer rather than the current use as a last resort.
Tailoring Image Contrast for Cellular Magnetic Resonance Imaging using Gadolinium Chelates and Superparamagnetic Iron Oxide Particles.
Kim YB
Mol Imaging Biol · 2025 Oct · PMID 40841497 · Publisher ↗
To investigate magnetic relaxation properties of the tailored contrast using paramagnetic gadolinium (Gd) chelates and superparamagnetic iron oxide particles (SPIOs) for cellular magnetic resonance imaging. The study inc...
To investigate magnetic relaxation properties of the tailored contrast using paramagnetic gadolinium (Gd) chelates and superparamagnetic iron oxide particles (SPIOs) for cellular magnetic resonance imaging. The study included three different exposed environments with two different characteristic contrast agents which used gadodiamide (Omniscan; Gd-DTPA-BMA) and ferumoxide (Feridex; SPIO) in C6 brain cancer cells. Based on the minimal mutual interaction between these two agents in vitro, we examined the possibility of using mixture of cells that are separately labeled with two contrast agents or using concurrently labeled cells with different concentrations of the two contrast agents. In order to characterize the MR relaxation properties, aqueous solutions containing various concentrations of the two contrast agents were prepared as well as Ficoll solution suspensions containing labeled cells by different labeling schemes and subsequently investigated R and R relaxation rates. The tailored contrast can be created by concurrent labeling of the two contrast agents as well as combining separately labeled cells with the two contrast agents. The proposed method would be applied to generate tailored contrast for efficient detection of magnetically-labeled cells in molecular imaging and cell-based therapy.
Advances in the Molecular Imaging of Sarcoma: An Emphasis on Metabolic Imaging.
Jonnakuti S, Naseer R, Ng SJ … +4 more , Lau HC, Jia L, Mirbod M, Ayubcha C
Mol Imaging Biol · 2025 Oct · PMID 40830327 · Publisher ↗
PURPOSE: Sarcomas, malignancies of mesenchymal origin, present significant diagnostic and therapeutic challenges due to their heterogeneity and low incidence. This review aims to examine the evolving role of fluorodeoxyg...
PURPOSE: Sarcomas, malignancies of mesenchymal origin, present significant diagnostic and therapeutic challenges due to their heterogeneity and low incidence. This review aims to examine the evolving role of fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the management of soft tissue and musculoskeletal sarcomas. Specifically, it seeks to evaluate 18F-FDG PET/CT's utility in detecting metastatic lesions, differentiating benign from malignant tumors, and assessing treatment responses. PROCEDURES: A comprehensive review of the literature was conducted to analyze advancements in PET imaging for sarcomas. Emphasis was placed on 18F-FDG PET/CT's role in complementing conventional imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Key aspects of PET imaging in musculoskeletal and cardiac tumors were examined, including its sensitivity and specificity in identifying metastases and its metabolic characterization of various tumor types. RESULTS: 18F-FDG PET/CT has demonstrated high sensitivity and specificity in detecting metastatic sarcoma lesions and grading musculoskeletal tumors, such as osteosarcoma, chondrosarcoma, and Ewing sarcoma. Its ability to provide metabolic insights has enhanced differentiation between benign and malignant tumors, including myxomas, lipomas, angiosarcomas, and leiomyosarcomas. Furthermore, in primary and secondary cardiac tumors, 18F-FDG PET/CT has proven valuable for treatment planning by offering detailed metabolic characterization. CONCLUSIONS: 18F-FDG PET/CT serves as a critical imaging modality in the diagnosis, staging, and treatment monitoring of sarcomas. By complementing conventional imaging techniques, it enhances the accuracy of tumor characterization and facilitates improved clinical decision-making. Its application in both musculoskeletal and cardiac sarcomas underscores its growing significance in oncologic imaging, making it a valuable tool in optimizing patient outcomes.
Enhanced Visualisation of Colorectal Tumours via Topical Application of EMI-137 in a Methylcellulose-Based Formulation: An ex vivo Feasibility Study.
Zonoobi E, Linders DGJ, Harmsen S … +16 more , Luna MRR, Bhairosingh SS, Almandawi DDA, Van Vlierberghe RLP, Nogaitzig MWJ, Portal C, Crobach SALP, Diana M, Noordam G, van den Burg D, Peters EEM, Marinelli AWKS, Tollenaar RAEM, Hilling DE, Kuppen PJK, Vahrmeijer AL
Mol Imaging Biol · 2025 Oct · PMID 40826308 · Full text
BACKGROUND: Fluorescence-guided molecular imaging may improve colorectal cancer (CRC) patient outcomes by enabling early detection and better surgical treatment, relying on developing targeted fluorescent tracers to high...
BACKGROUND: Fluorescence-guided molecular imaging may improve colorectal cancer (CRC) patient outcomes by enabling early detection and better surgical treatment, relying on developing targeted fluorescent tracers to highlight tumours. This study investigates visualising primary colon tumours by topically applying EMI-137, a targeted fluorescent tracer designed to bind to c-Met receptor. We introduce a novel viscous formulation to enhance the tracer's performance, aiming for a clear, robust fluorescent signal by improving contact with mucosal surface of ex vivo colon specimens. METHODS: We evaluated fluorescence properties of EMI-137 in phosphate-buffered saline (PBS) and in methylcellulose (m-cellulose) and determined emission spectrum of the tracer in both formulations. Flow cytometry was used to determine EMI-137's specificity for c-Met receptor and its optimal concentration. Live-cell imaging visually confirmed EMI-137's fluorescence signal for the c-Met receptor, highlighting its distinctive characteristics across various solvents. In a prospective cohort study, freshly excised colon cancer specimens were incubated with EMI-137 in PBS or m-cellulose. Specimens underwent a meticulous washing process. Near-infrared fluorescence imaging was performed and compared with histopathological analysis to validate detection accuracy. RESULTS: Fluorospectrometry showed that m-cellulose enhanced EMI-137's fluorescence intensity compared to PBS. Flow cytometry showed dose-dependent binding of EMI-137 in HT-29 cells, with an optimum at 500 nM. Microscopy confirmed targeting of c-Met receptors. Topical EMI-137 dissolved in m-cellulose visualised colon tumours effectively, resulting in a high tumour-to-background ratio. Histopathological analysis confirmed c-Met expression in these colon tumours. CONCLUSION: EMI-137 in a novel viscous vehicle effectively imaged c-Met expressing colon tumors, potentially facilitating fluorescent-guided tumor imaging.
Evaluation of Indocyanine Green Derivatives with Sulfonic Acid and Carboxylic Acid Groups at the Benzoindolenine Moiety for Antibody-Based Tumor Imaging.
Nakajima K, Maeta H, Takakura H … +3 more , Tsuchiya K, Ohira T, Ogawa M
Mol Imaging Biol · 2025 Oct · PMID 40796715 · Publisher ↗
PURPOSE: In target-specific cancer imaging, antibodies and their fragments are conjugated with fluorescent dyes to work as targeting molecules. We have recently developed indocyanine green (ICG) derivatives with anionic...
PURPOSE: In target-specific cancer imaging, antibodies and their fragments are conjugated with fluorescent dyes to work as targeting molecules. We have recently developed indocyanine green (ICG) derivatives with anionic functional groups at the benzoindolenine moiety. When the ICG derivatives are used for antibody-based imaging, the chemical characteristics of the conjugated dyes may influence the pharmacokinetics of the targeting molecules. Therefore, in this study, we evaluated the in vivo pharmacokinetics of IgG and Fab conjugated with the ICG derivatives bearing anionic functional groups. PROCEDURES: A linker for conjugation was introduced into the methine chain of ICG and ICG derivatives possessing sulfonic acid (SC-Cy) or carboxylic acid (CC-Cy) groups at the benzoindolenine moiety. ICG, SC-Cy, or CC-Cy was conjugated with IgG, innate trastuzumab, and its Fab fragment. To evaluate the pharmacokinetics of these IgG-dyes and Fab-dyes, in vivo fluorescence imaging was performed in tumor-bearing mice at 0.25-96 h after intravenous administration of the imaging agents. RESULTS: The three IgG-dyes exhibited similar pharmacokinetics and tumor accumulation profiles post injection. Thus, the differences in the dye's chemical properties had minimal influence when the ICG derivatives were conjugated with IgG. In contrast, the pharmacokinetics and tumor accumulation profiles of the Fab-dyes were remarkably different. While Fab-SC-Cy exhibited high accumulation in the kidney but no accumulation in the tumors, Fab-CC-Cy showed higher tumor accumulation. This could be attributed to the excessively high negative charge density in the benzoindolenine moiety of SC-Cy, which influenced the excretion route of the Fab fragment. CONCLUSIONS: The IgG conjugated with SC-Cy or CC-Cy dyes exhibited favorable pharmacokinetics profiles. In contrast, Fab-CC-Cy demonstrated superior performance in tumor imaging compared to Fab-SC-Cy. Our findings suggest that introducing anionic functional groups into the benzoindolenine moiety of ICG could lead to the development of near-infrared dyes that could be useful in antibody-based tumor imaging.
PET Imaging of Diabetes-Induced Alterations in Metabolism and Immune Activation.
Lynch SE, Alsheikh HM, Song PN … +7 more , Parker CC, Zhang Y, Yates CC, Larimer BM, Lapi SE, Shevde LA, Sorace AG
Mol Imaging Biol · 2025 Oct · PMID 40796714 · Full text
INTRODUCTION: Obesity and type 2 diabetes (T2D) influence the tumor microenvironment by altering glucose metabolism, which has been shown to decrease immune cell infiltration and activation. Positron emission tomography...
INTRODUCTION: Obesity and type 2 diabetes (T2D) influence the tumor microenvironment by altering glucose metabolism, which has been shown to decrease immune cell infiltration and activation. Positron emission tomography (PET) imaging provides a non-invasive method to detect molecular markers of immune populations in the tumor microenvironment and systemic organs. The goal of this study is to utilize advanced molecular imaging to quantify differences in innate and adaptive immune responses in diabetic obese mice systemically and within the tumor microenvironment. METHODS: 5-6-week-old female C57BL6/J mice were placed on a high-fat diet (HFD) composed of 60% kcal fat or control low-fat diet with 10% kcal fat. Animals were treated with subsequent low doses of streptozotocin to induce T2D and blood glucose was monitored. Following induction of diabetes, E0771-luc + cells were implanted into the 4th mammary fat pad and allowed to grow to a tumor volume of 100mm. PET imaging was acquired over the course of 5 days with the following tracers: [F]-FDG PET for glucose metabolism, [Ga]Ga-RP832c (CD206) PET for M2 macrophages, and [Ga]Ga-GZP PET for granzyme B, an indicator of effector cell activation, and [F]-DPA-714 PET for neuroinflammation. Regions of interest were identified for the tumor, brain, kidneys, heart, muscle, brown adipose tissue (BAT), to characterize differences in important organs and tumor tissue. Metrics of standardized uptake value (SUV) were extracted from imaging data including mean, max, peak, and tumor-to-background ratios. Following the final imaging timepoint, tumors were extracted for biological characterization via flow cytometry. RESULTS: Diabetic obese mice have no difference in tumor glucose metabolism, but have decreased FDG uptake in the brain and BAT compared to controls. Obesity and T2D systemically affect innate and adaptive immune infiltration and activation including significantly increased RP832c and GZP in muscle, heart, brain, and BAT. Hyperglycemic tumors had trending decreases in GZP SUV and increased RP832c SUV. Flow cytometry shows diabetic obese tumors have a significant increase in CD206 + macrophages and no significant difference in GZB + CD8 + T cells compared to controls. CONCLUSION: PET imaging reveals that obesity and T2D alter glucose metabolism and immune activation while suppressing tumor-immune activation in diabetic obese mice both within the tumor microenvironment and systemically.
Fibrotic Disease: from Signaling Pathways and Biomarkers to Molecular Imaging.
Ghazaiean M, Riss PJ, Mardanshahi A … +1 more , Molavipordanjani S
Mol Imaging Biol · 2025 Oct · PMID 40790290 · Publisher ↗
Fibrotic diseases are characterized by excessive accumulation of extracellular matrix (ECM) components following tissue injury, ultimately leading to organ dysfunction and failure. The progression of fibrosis is governed...
Fibrotic diseases are characterized by excessive accumulation of extracellular matrix (ECM) components following tissue injury, ultimately leading to organ dysfunction and failure. The progression of fibrosis is governed by complex molecular signaling pathways, including TGF-β, PDGF, FGF, CTGF, VEGF, and many others, which regulate myofibroblast activation, ECM production, and tissue remodeling. Traditional diagnostic modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and biopsy are limited in their ability to distinguish active fibrogenesis from established fibrosis or detect early molecular changes. Recent advances in molecular imaging such as the development of targeted radiotracers and MRI contrast agents-have enabled more precise detection and characterization of fibrotic processes at both preclinical and clinical levels. The integration of molecular imaging with targeted probes holds promise for improving early diagnosis, guiding therapeutic strategies, and advancing clinical management of fibrosis. This review presents a comprehensive overview of the molecular mechanisms underlying fibrogenesis, highlights key signaling pathways and biomarkers, and discusses current and emerging molecular imaging agents for fibrotic diseases diagnosis and monitoring.
CREBBP Mutation as a Culprit for Negative SSTR2 PET in Neuroendocrine Tumors.
Haj-Mirzaian A, Esfahani SA, Mahmood U … +1 more , Heidari P
Mol Imaging Biol · 2025 Oct · PMID 40779286 · Full text
PURPOSE: This study aimed to elucidate the molecular and genetic factors contributing to negative Ga-DOTATATE PET imaging in neuroendocrine tumors (NETs). By integrating whole exome sequencing (WES) and single-cell RNA s...
PURPOSE: This study aimed to elucidate the molecular and genetic factors contributing to negative Ga-DOTATATE PET imaging in neuroendocrine tumors (NETs). By integrating whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq), we sought to unravel the interplay between negative results of Ga-DOTATATE PET and genetic mutations in NETs. METHODS: A total of 18 patients with lung, ileal, or pancreatic NETs who underwent Ga-DOTATATE and F-FDG PET/CT scans as part of their initial diagnostic workup were retrospectively reviewed. WES analysis was conducted to investigate the genetic profile of circulating tumor cells of patients with negative Ga-DOTATATE scans. Leveraging scRNA-seq and single-cell somatic variant calling analysis, we compared the mutation burden and genetic hallmarks of NET cells with high /positive SSTR2 expression to those with negative/low SSTR2 expression. RESULTS: Our analysis identified an association between negative Ga-DOTATATE scans and reduced survival rates, regardless of tumor grade. WES highlighted a predominance of missense mutations, including CREBBP mutation, particularly in patients with negative PET results (incidence of %67 vs. %0). We observed a deleterious mutation in the SSTR2, likely accounting for the observed negative PET scans (incidence of %33). Single-cell single nucleotide variant (SNV) analysis showed that the total unique mutation burden in cells with negative/low SSTR2 expression was significantly higher compared to cells with positive/high expression; and notably, the CREBBP mutation was observed in more than 50% of patients and approximately 35% of NET cells. These results indicate that the frequency of CREBBP mutations is nearly as high as other well-known NET mutations such as MEN1, PTEN, and RB1. Additionally, CREBBP mutations are significantly more frequent in tumors with negative/low SSTR2 expression. CONCLUSION: This study suggests that CREBBP mutations in NETs may potentially alter SSTR2 expression, indicating that patients with the mutated CREBBP genotype may not be suitable candidates for SSTR2-targeted PET imaging and radionuclide therapy.
Enhancing the Half-Life of ODAP-Urea Based Radioligands by Incorporating Albumin-Binding Moieties.
Chen XY, Zhang Y, Duan X … +5 more , Zhang J, Zhang Z, Yang X, Wei ZX, He ZX
Mol Imaging Biol · 2025 Oct · PMID 40775565 · Publisher ↗
PURPOSE: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) is a promising approach to treating metastatic castration-resistant prostate cancer (mCRPC). With the emergence of oxalyldiaminopropioni...
PURPOSE: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) is a promising approach to treating metastatic castration-resistant prostate cancer (mCRPC). With the emergence of oxalyldiaminopropionic acid urea (ODAP-Urea) based radioligands targeting PSMA, novel paradigms focused on PSMA-RLT are garnering attention. This study aims to assess potentially novel ODAP-Urea-based radioligands prepared for PSMA-RLT. METHODS: Albumin binding moieties (ABMs) were selected for optimization. Candidates were evaluated in vitro and subsequently investigated through biodistribution and imaging studies in 22Rv1 tumor-bearing mice. RESULTS: We synthesized five novel ODAP-Urea-based derivatives (CXY-18, CXY-19, CXY-20, CXY-21, CXY-23) with specific ABM. All compounds demonstrated high affinities for PSMA (K values ranging from 0.21 nM to 3.6 nM) and strong human albumin protein binding abilities (83.4 ± 1.6% to 94.6 ± 0.4%). [Ga]Ga-CXY-18 (CXY-18) PET/CT exhibited the highest tumor uptake and blood retention properties. Moreover, the internalization of [Ga]Ga-CXY-18 in the 22Rv1 cell line (23.81 ± 1.67%) exceeded that of [Ga]Ga-PSMA-617 (9.99 ± 0.98%). Biodistribution studies confirmed prolonged blood retention and enhanced tumor uptake with [Lu]Lu-CXY-18, peaking at 48 h post-injection (4 h: 27.22 ± 3.61%ID/g; 24 h: 30.61 ± 4.96%ID/g; 48 h: 33.92 ± 2.98%ID/g; 96 h: 30.97 ± 1.87%ID/g; 192 h: 9.03 ± 3.49%ID/g). CONCLUSION: Our study indicates that CXY-18 possesses high PSMA specificity and tumor uptake, underscoring its promising potential for PSMA-RLT using 4-IBA.
Reengineered Anti-CD4 Cys-diabody Variants for Zr-immunoPET of CD4 T Cells in Immunocompetent Mice.
Salazar FB, Tavaré R, Ökten A … +3 more , Kujawski M, Wu AM, Zettlitz KA
Mol Imaging Biol · 2025 Oct · PMID 40775564 · Full text
PURPOSE: CD4 T cells (T helper and T reg) play an important role in the immune system and are influential in autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) and cancer (antitumor immunity). N...
PURPOSE: CD4 T cells (T helper and T reg) play an important role in the immune system and are influential in autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) and cancer (antitumor immunity). Non-invasive, whole-body anti-CD4 immunoPET can provide dynamic and spatial information (localization, proliferation, and migration) on CD4 T cells. The cys-diabody format enables site-specific radiolabeling and rapid renal clearance, which results in high-contrast images at early time points. PROCEDURES: In this work, an anti-CD4 cys-diabody based on the hybridoma GK1.5 was reengineered by CDR-grafting (GK1.5 FR cDb) for higher expression in mammalian cell lines. An N-glycosylation motif in the variable light chain domain framework was removed by site-directed mutagenesis, resulting in GK1.5 N80D cDb. To investigate the impact of the variable domain glycan on the in vivo biodistribution and pharmacokinetics, both cys-diabodies were site-specifically conjugated with deferoxamine-maleimide and radiolabeled by chelation of zirconium-89. Serial immunoPET/CT imaging was used for non-invasive, whole-body assessment of specific targeting, biodistribution, and differential clearance of the two novel anti-CD4 cys-diabodies. RESULTS: The anti-CD4 cys diabody was successfully re-engineered by CDR-grafting (GK1.5 FR cDb) and aglycosylation (GK1.5 N80D cDb), resulting in a higher expression yield (~ tenfold increase) without impacting antigen specificity or affinity. Both cys-diabody variants were successfully Zr-radiolabeled with similar specific activity and radiochemical purity. ImmunoPET imaging of Zr-GK1.5 FR cDb and Zr-GK1.5 N80D cDb in immunocompetent mice showed CD4 antigen-specific lymphoid tissue uptake in vivo. Zr-GK1.5 FR cDb exhibited rapid hepatic clearance, resulting in significantly reduced uptake in lymph nodes and the spleen. Removal of the N-glycosylation motif in Zr-GK1.5 N80D cDb restored diabody-typical biodistribution (renal clearance), resulting in higher target tissue uptake. CONCLUSION: The novel reengineered anti-CD4 GK1.5 N80D cDb overcomes the previous production yield bottleneck and provides same-day Zr-immunoPET imaging for non-invasive, whole-body visualization of murine CD4 T cells.
In vivo Multimodal Magnetic Particle Imaging for Early Detection of Ischemic Stroke in Tree Shrews.
Zhang B, Zhu T, Zhang H … +15 more , Yu X, He J, Liu S, Liu Y, Wei Z, Hu C, Zhang Y, Huang H, Qiu M, Jin R, Li H, Xie H, Wang J, Hui H, Tian J
Mol Imaging Biol · 2025 Oct · PMID 40770598 · Publisher ↗
PURPOSE: Ischemic stroke is a significant threat to human life and health, and timely diagnosis is essential for improving patient outcomes. Magnetic Particle Imaging (MPI), as an emerging high-sensitivity imaging techno...
PURPOSE: Ischemic stroke is a significant threat to human life and health, and timely diagnosis is essential for improving patient outcomes. Magnetic Particle Imaging (MPI), as an emerging high-sensitivity imaging technology, holds significant potential for the diagnosis of ischemic stroke. It is necessary to conduct multimodal MPI research based on the characteristics of the animal model and the detection needs of ischemic stroke. PROCEDURES: We used tree shrews, which have a close phylogenetic relationship with primates, as experimental subjects and established a photothrombotic (PT) stroke model. Considering the body size of tree shrews and the high-sensitivity detection requirements for ischemic stroke, a dedicated MPI receiving system for tree shrews was developed based on the primate brain MPI equipment. After validating the MPI system's performance, multimodal MPI fusion imaging of the tree shrew brain was performed by combining magnetic resonance imaging (MRI) and computed tomography (CT). RESULTS: The sensitivity of the receiving system for tree shrews is 0.017 mg Fe/mL, which is 8 times higher than that of the original system. Within one hour after the establishment of the PT stroke model, the MPI signal intensity in ischemic stroke tree shrews was approximately 25% lower than in the control group, while MRI showed no significant differences. On the 6th and 12th days after ischemic stroke onset, MRI images revealed clear lesion locations. Anatomical results of the tree shrew brain revealed significant lesions, confirming the successful establishment of the PT stroke model. CONCLUSIONS: The dedicated MPI receiving system developed in this study significantly enhanced MPI sensitivity. The multimodal MPI imaging platform integrates the advantages of MRI and CT structural imaging based on high-sensitivity detection, enabling early detection of ischemic stroke in tree shrews.
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