Molecular Imaging And Biology[JOURNAL]
Sun
200 papers
Prospective Comparison of [F]FDG and [F]AIF-FAPI-74 PET/CT in the Evaluation of Potentially Resectable Pancreatic Ductal Adenocarcinoma.
Yun WG, Gil J, Choi H … +8 more , Han Y, Jung HS, Cho YJ, Suh M, Kwon W, Lee YS, Cheon GJ, Jang JY
Mol Imaging Biol · 2024 Dec · PMID 39365411 · Full text
PURPOSE: Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([F]FDG...
PURPOSE: Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [F]FDG and [F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC. PROCEDURES: Between 2021 and 2022, twenty participants with newly diagnosed potentially resectable PDAC were enrolled. After the initial evaluation with pancreatic CT, [F]FDG PET/CT, and [F]AIF-FAPI-74 PET/CT, treatment strategies were determined considering the participant's general status, clinical staging, and resectability. Pathological information from the surgical specimens was only available in 17 participants who underwent curative-intent surgery. Head-to-head comparisons of quantitative radiotracer uptake and diagnostic performance were performed among imaging modalities. RESULTS: [F]AIF-FAPI-74 PET/CT showed a significantly higher maximum standardized uptake value than [F]FDG PET/CT did in evaluating primary pancreatic lesions (median [interquartile range]; 12.6 [10.7-13.7] vs. 6.3 [4.8-9.2]; P < 0.001). In contrast, [F]AIF-FAPI-74 PET/CT showed a significantly lower mean standardized uptake value than [F]FDG PET/CT did in evaluating background organ (median [interquartile range]) 0.8 [0.7-0.9] vs. 2.6 [2.3-2.7]; P < 0.001). In addition, the sensitivity of [F]AIF-FAPI-74 PET/CT in detecting metastatic lymph nodes was higher than that of [F]FDG PET/CT (50.0% vs. 0.0%; P = 0.026). CONCLUSION: This study demonstrated that [F]AIF-FAPI-74 PET/CT could improve the clinical staging of potentially resectable PDAC.
Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections : Toxin-Derived Optical Probes for Neuroimaging.
Bijjam R, Shorter S, Bratt AM … +3 more , O'Leary VB, Ntziachristos V, Ovsepian SV
Mol Imaging Biol · 2024 Dec · PMID 39348040 · Full text
Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neu...
Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neurotransmitter release at presynaptic terminals have attracted much interest in experimental neurobiology and clinical research. Fused with reporter proteins or labelled with fluorophores, BoNTs and TeTX and their non-toxic fragments also offer remarkable opportunities to visualize cellular processes and functions in neurons and synaptic connections. This study presents the state-of-the-art optical probes derived from BoNTs and TeTX and discusses their applications in molecular and synaptic biology and neurodevelopmental research. It reviews the principles of the design and production of probes, revisits their applications with advantages and limitations and considers prospects for future improvements. The versatile characteristics of discussed probes and reporters make them an integral part of the expanding toolkit for molecular neuroimaging, promoting the discovery process in neurobiology and translational neurosciences.
Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.
Linders DGJ, Bijlstra OD, Fallert LC … +12 more , Dekker-Ensink NG, March TL, Pool M, Walker E, Straight B, Basilion JP, Bogyo M, Burggraaf J, Hilling DE, Vahrmeijer AL, Kuppen PJK, Crobach ASLP
Mol Imaging Biol · 2024 Dec · PMID 39331316 · Full text
PURPOSE: Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their pot...
PURPOSE: Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their potential as a target for tumor imaging. In particular cathepsin B (CTSB), L (CTSL), and S (CTSS) are used as targets for near-infrared (NIR) fluorescence imaging (FI), a technique that allows real-time intraoperative tumor visualization and resection margin assessment. Therefore, this immunohistochemical study explores CTSB, CTSL, and CTSS expression levels in a large breast cancer patient cohort, to investigate in which BCa patients the use of cathepsin-targeted NIR FI may have added value. PROCEDURES: Protein expression was analyzed in tumor tissue microarrays (TMA) of BCa patients using immunohistochemistry and quantified as a total immunostaining score (TIS), ranging from 0-12. In total, the tissues of 557 BCa patients were included in the TMA. RESULTS: CTSB, CTSL, and CTSS were successfully scored in respectively 340, 373 and 252 tumors. All tumors showed CTSB, CTSL, and/or CTSS expression to some extent (TIS > 0). CTSB, CTSL, and CTSS expression was scored as high (TIS > 6) in respectively 28%, 80%, and 18% of tumors. In 89% of the tumors scored for all three cathepsins, the expression level of one or more of these proteases was scored as high (TIS > 6). Tumors showed significantly higher cathepsin expression levels with advancing Bloom-Richardson grade (p < 0.05). Cathepsin expression was highest in estrogen receptor (ER)-negative, human epidermal growth factor receptor 2(HER2)-positive and triple-negative (TN) tumors. There was no significant difference in cathepsin expression between tumors that were treated with neoadjuvant systemic therapy and tumors that were not. CONCLUSIONS: The expression of at least one of the cysteine cathepsins B, L and S in all breast tumor tissues tested suggests that cathepsin-activatable imaging agents with broad reactivity for these three proteases will likely be effective in the vast majority of breast cancer patients, regardless of molecular subtype and treatment status. Patients with high grade ER-negative, HER2-positive, or TN tumors might show higher imaging signals.
Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors.
Nandi A, Nakano M, Brašić JR … +7 more , Brinson ZS, Kitzmiller K, Mathur A, Mohamed M, Roberts J, Wong DF, Kuwabara H
Mol Imaging Biol · 2024 Dec · PMID 39313673 · Publisher ↗
PURPOSE: Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dime...
PURPOSE: Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BP) in rodent PET studies. PROCEDURES: PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BP in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT. RESULTS: The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BP in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter. CONCLUSIONS: The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BP in proportion to errors of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners.
Chemokine Receptor 4-Targeted PET/CT with [Ga]pentixather in Newly Diagnosed Multiple Myeloma: a Comparative Study with [Ga]pentixafor PET/CT.
Yang Q, Zhang F, Hao Z … +2 more , Zhuang J, Huo L
Mol Imaging Biol · 2024 Dec · PMID 39304574 · Publisher ↗
PURPOSE: This study aimed to compare the detection rate of [Ga]pentixather PET/CT and [Ga]pentixafor PET/CT in newly diagnosed multiple myeloma (NDMM) patients, and to explore the value of [Ga]pentixather PET/CT for tumo...
PURPOSE: This study aimed to compare the detection rate of [Ga]pentixather PET/CT and [Ga]pentixafor PET/CT in newly diagnosed multiple myeloma (NDMM) patients, and to explore the value of [Ga]pentixather PET/CT for tumor load assessment. METHODS: Nineteen NDMM Patients were prospectively recruited and underwent both [Ga]pentixather PET/CT and [Ga]pentixafor PET/CT. A positive PET scan was defined as the presence of PET-positive focal bone lesions, paraskeletal disease, extramedullary plasmacytoma, or diffuse bone marrow uptake. Lesion numbers, SUVmax and PET-related tumor burden values were compared. The correlations between PET-related tumor burden and clinical risk stratification were analyzed. RESULTS: [Ga]pentixather PET/CT showed a tendency of higher positive rate compared with [Ga]pentixafor PET/CT [94.7% (18/19) vs. 78.9% (15/19), p > 0.05]. Among 14 patients with 151 matched focal bone lesions, [Ga]pentixather PET detected more or equal number of lesions in 13 patients, and demonstrated higher uptake value than Ga-pentixafor PET [SUVmax, 16.8 (9.0, 23.8) vs. 13.4 (6.5, 20.4), p < 0.001]. For PET related-tumor burden, positive correlations of total bone marrow uptake (TBmU) (r = 0.9540, p < 0.0001) and SUVmean of total bone marrow (r = 0.9632, p < 0.0001) in two PET scans were observed. Higher TBmU [7864.9 (5549.2, 11,616.2) vs. 5383.4(4102.7, 11,041.8), p < 0.001], SUVmean of total bone marrow [1.4 (1.1, 2.2) vs. 1.1 (0.7, 2.1), p < 0.001] were demonstrated on [Ga]pentixather PET than [Ga]pentixafor PET. And the level of TBmU in [Ga]pentixather PET and [Ga]pentixafor PET were both elevated in Durie-Salmon Staging (DSS) III than DSS I (p < 0.01). CONCLUSIONS: [Ga]pentixather PET/CT performed a non-inferior capability for tumor detection compared to [Ga]pentixafor PET/CT in NDMM patients. [Ga]pentixather PET/CT can assess tumor load in MM patients and depict a significantly higher PET-related total tumor burden than [Ga]pentixafor PET/CT.
Usefulness of the Primary Tumor Standardized Uptake Value of Iodine-123 Metaiodobenzylguanidine for Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma.
Hirahara M, Nakajo M, Kitazano I … +6 more , Jinguji M, Tani A, Takumi K, Kamimura K, Tanimoto A, Yoshiura T
Mol Imaging Biol · 2024 Dec · PMID 39294365 · Full text
PURPOSE: To examine the usefulness of semi-quantitative analysis using the standardized uptake value (SUV) of iodine-123 metaiodobenzylguanidine ([I]-MIBG) for predicting metastatic potential in patients with pheochromoc...
PURPOSE: To examine the usefulness of semi-quantitative analysis using the standardized uptake value (SUV) of iodine-123 metaiodobenzylguanidine ([I]-MIBG) for predicting metastatic potential in patients with pheochromocytoma (PHEO) and paraganglioma (PGL). PROCEDURES: This study included 18 PHEO and 2 PGL patients. [I]-MIBG visibility and SUV-related parameters (SUVmax, SUVmean, tumor volume of [I]-MIBG uptake [TV_MIBG], and total lesion [I]-MIBG uptake) were compared with the pathological grading obtained using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP), which are used to predict metastatic potential. The PASS scores were categorized as < 4 and ≥ 4. Based on the GAPP scores, PHEOs/PGLs were categorized as follows: well, moderately, and poorly differentiated tumors. The Mann-Whitney U test or Spearman's rank correlation was used to assess differences or associations between two quantitative variables. RESULTS: All PHEOs/PGLs were visualized on [I]-MIBG scintigraphy. There were 16 PASS < 4 and 4 PASS ≥ 4 tumors. Moreover, 11 and 9 tumors were well and moderately differentiated, respectively. The uptake scores and SUV-related parameters significantly differed between tumors with a PASS score of < 4 and those with a PASS score of ≥ 4 (each, p > 0.05). Moderately differentiated tumors had significantly higher uptake scores and SUV-related parameters except TV_MIBG than well-differentiated tumors (each, p < 0.05). The GAPP score was positively correlated with the uptake scores and SUV-related parameters (each, p < 0.05) except TV_MIBG. CONCLUSIONS: The primary tumor [I]-MIBG uptake assessed using SUV-related parameters can be an imaging tool for predicting metastatic potential in patients with PHEO/PGL.
Radioimaging Foam Cells Infiltrating Atherosclerotic Plaques in Mice Using I-labeled oxLDL as a Radiotracer.
Izawa M, Kawashima H, Okuno Y … +8 more , Nakaya J, Takeda M, Harada K, Yamada Y, Nishimura K, Ishihara K, Akiba S, Takata K
Mol Imaging Biol · 2024 Dec · PMID 39287887 · Publisher ↗
Bioimaging such as magnetic resonance is used to monitor atherosclerotic plaques consisting of foam cells, which are derived from macrophages that have ingested oxidized low-density lipoprotein (oxLDL). However, the curr...
Bioimaging such as magnetic resonance is used to monitor atherosclerotic plaques consisting of foam cells, which are derived from macrophages that have ingested oxidized low-density lipoprotein (oxLDL). However, the current bioimaging techniques are not highly specific and sensitive in detecting foam cells, calling for the development of higher precision foam cell detection probes. Here, we investigated the utility of iodine-125-labeled oxLDL (I-oxLDL) as a prototype radiotracer in the radioimaging of foam cells infiltrating atherosclerotic plaques. Mouse bone marrow-derived macrophages (BMDMs) were used to analyze oxLDL uptake. Atherosclerosis mouse model was injected with I-oxLDL and DiI-labeled oxLDL (DiI-oxLDL). Accumulation of I-oxLDL and DiI-oxLDL in foam cells infiltrating atherosclerotic plaques was examined using Oil Red O (ORO) staining, autoradiography, and fluorescent immunohistochemistry. BMDMs phagocytosed oxLDL/I-oxLDL via CD36, but not LDL/I-LDL. The radioactive signal from I-oxLDL phagocytosed by the BMDMs could be detected for at least 3 days. In atherosclerosis mouse model, atherosclerotic plaques formed in the aortic arches and valves. The radioactive signal of the injected I-oxLDL was detected in atherosclerotic plaques of the aortic arch, and its intensity was positively correlated with the lesion size. Furthermore, the DiI-oxLDL fluorescent signals were detected in foam cells accumulating in atherosclerotic plaques. Thus, we found that I-oxLDL can be used as a radiotracer in the radioimaging of foam cells in atherosclerotic plaques by autoradiography, suggesting its potential future applications in bioimaging methods such as single-photon emission computed tomography.
Ultrasound Imaging of Macrophages Intracellularly Labelled with Biosynthetic Gas Vesicles.
Xue R, Liu Z, Liu L … +2 more , Sun S, Gong Z
Mol Imaging Biol · 2024 Oct · PMID 39198330 · Publisher ↗
PURPOSE: This study aimed to develop a novel method for real-time imaging to track macrophages and to make it possible to visually track their dynamic features. PROCEDURES: The archaeon Halobacterium NRC-1 was cultured i...
PURPOSE: This study aimed to develop a novel method for real-time imaging to track macrophages and to make it possible to visually track their dynamic features. PROCEDURES: The archaeon Halobacterium NRC-1 was cultured in an ATCC medium. Buoyant cells were allowed to produce biosynthetic gas vesicles (GVs), and isolated GVs were collected after lysis. Gas vesicle-labelled macrophages (GV@RAWs) were obtained by incubating macrophage (RAW 264.7) cells with GVs. The ability of GV@RAWs to track macrophages in real-time for a long term was assessed using a high-frequency ultrasound imaging system. RESULTS: We successfully synthesised and isolated GV@RAWs by co-incubating them with RAW 264.7. The results showed that GV@RAW produced significant ultrasound signals without affecting cell survival and could achieve real-time imaging for up to 3 days in vitro. CONCLUSION: This research provides a new way to achieve long-term real-time imaging of macrophages, opening up new possibilities for immune response research, clinical diagnosis and therapeutic strategies for inflammatory diseases.
Correction: Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers.
Leach BI, Lister D, Adams SR … +5 more , Bykowski J, Schwartz AB, McConville P, Dimant H, Ahrens ET
Mol Imaging Biol · 2024 Oct · PMID 39192060 · Publisher ↗
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Development of Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2.
Omweri JM, Saini S, Houson HA … +4 more , Tekin V, Pyles JM, Parker CC, Lapi SE
Mol Imaging Biol · 2024 Oct · PMID 39192059 · Full text
PURPOSE: Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission T...
PURPOSE: Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 (Mn, t = 5.6 d, β = 29.6%, E(β) = 242 keV) is suitable for imaging at longer time points providing a complementary technique to Zirconium-89 (Zr, t = 3.3 d, β = 22.7%, E(β) = 396 keV)) because of its long half-life and low positron energy. To exploit these properties, we aimed to investigate suitable bifunctional chelators that could be readily conjugated to antibodies and labeled with Mn under mild conditions using trastuzumab as a proof-of-concept. PROCEDURES: Trastuzumab was incubated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 1-Oxa-4,7,10-tetraazacyclododecane-5-S-(4-isothiocyantobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A), and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA) at a tenfold molar excess. The immunoconjugates were purified, combined with [Mn]MnCl at different ratios, and the labeling efficiency was assessed by iTLC. The immunoreactive fraction of the radiocomplex was determined through a Lindmo assay. Cell studies were conducted in HER2 + (BT474) and HER2- (MDA-MB-468) cell lines followed by in vivo studies. RESULTS: Trastuzumab-Oxo-DO3A was labeled within 30 min at 37 °C with a radiochemical yield (RCY) of 90 ± 1.5% and with the highest specific activity of the chelators investigated of 16.64 MBq/nmol. The labeled compound was purified with a resulting radiochemical purity of > 98% and retained a 67 ± 1.2% immunoreactivity. DOTA and PCTA immunoconjugates resulted in < 50 ± 2.5% (RCY) with similar specific activity. Mouse serum stability studies of [Mn]Mn-Oxo-DO3A-trastuzumab showed 95% intact complex for over 5 days. Cell uptake studies showed higher uptake in HER2 + (12.51 ± 0.83% /mg) cells compared to HER2- (0.85 ± 0.10%/mg) cells. PET images of mice bearing BT474 tumors showed high tumor uptake that was consistent with the biodistribution (42.02 ± 2.16%ID/g, 14 d) compared to MDA-MB-468 tumors (2.20 ± 0.80%ID/g, 14 d). Additionally, both models exhibited low bone uptake of < 1% ID/g. CONCLUSION: The bifunctional chelator p-SCN-Bn-Oxo-DO3A is promising for the development of Mn radiopharmaceuticals as it was easily conjugated, radiolabeled at mild conditions, and illustrated stability for a prolonged duration both in vitro and in vivo. High-quality PET/CT images of [Mn]Mn-Oxo-DO3A-trastuzumab were obtained 14 d post-injection. This study illustrates the potential of [Mn]Mn-Oxo-DO3A for the evaluation of antibodies using PET imaging.
Zirconium- 89 Labeled Antibody K1-70 for PET Imaging of Thyroid-stimulating Hormone Receptor Expression in Thyroid Cancer.
Parent EE, Gleba JJ, Knight JA … +3 more , Kenderian SJ, Copland JA, Cai H
Mol Imaging Biol · 2024 Oct · PMID 39174789 · Publisher ↗
PURPOSE: Thyroid-stimulating hormone receptor (TSHR) is a G-protein coupled receptor that is highly expressed on benign and malignant thyroid tissues. TSHR binding and activation has long been a component of thyroid canc...
PURPOSE: Thyroid-stimulating hormone receptor (TSHR) is a G-protein coupled receptor that is highly expressed on benign and malignant thyroid tissues. TSHR binding and activation has long been a component of thyroid cancer molecular imaging and radiotherapy, by promoting expression of the sodium-iodide symporter (NIS) and incorporation of I-131 into thyroid hormones. Here, we report the radiosynthesis and preclinical evaluation of a Zirconium-89 (Zr) labeled TSHR antibody to serve as a positron emission tomography (PET) diagnostic correlate for therapeutic agents targeting TSHR without reliance on NIS. PROCEDURES: TSHR human monoclonal antibody K1-70 was conjugated to chelator desferrioxamine-p-benzyl-isothiocyanate, followed by labeling with Zr-89, yielding the radiotracer Zr-DFO-TSHR-Ab. The in vitro cellar uptake and binding affinity of Zr-DFO-TSHR-Ab were analyzed in three new TSHR stable overexpressing tumor cell lines and their corresponding wild types (WT) with low or no TSHR expression. Zr-DFO-TSHR-Ab PET/CT imaging of TSHR expression was evaluated in tumor mouse models bearing one TSHR-positive tumor and other negative control with or without the coinjection of antibody K1-70, and then verified by radiotracer biodistribution study and tumor immunohistochemistry (IHC). RESULTS: The conjugate DFO-TSHR-Ab was labeled with Zr-89 at 37 °C for 60 min and purified by PD-10 column in radiochemical yields of 68.8 ± 9.9%, radiochemical purities of 98.7 ± 0.8%, and specific activities of 19.1 ± 2.7 mCi/mg (n = 5). In vitro cell studies showed Zr-DFO-TSHR-Ab had significantly high uptake on TSHR expressing tumor cells with nanomolar affinity and high potency. Preclinical PET/CT imaging revealed that Zr-DFO-TSHR-Ab selectively detected TSHR expressing thyroid tumors and displayed improved in vivo performance with the coinjection of unlabeled TSHR antibody K1-70 leading to higher uptake in TSHR expressing tumors than parental WT tumors and physiologic tissues; this observation was confirmed by the biodistribution and immunostaining analyses. CONCLUSIONS: We synthesized Zr-labeled antibody K1-70 as a new radiopharmaceutical for PET imaging of TSHR. Zr-DFO-TSHR-Ab has high radioactive uptake and retention in TSHR expressing tumors and cleared quickly from most background tissues in mouse models. Our study demonstrated that Zr-DFO-TSHR-Ab has the potential for PET imaging of TSHR-positive thyroid cancer and monitoring TSHR-targeted therapy.
Administration of Aripiprazole Alleviates Memory Impairment and Restores Damaged Glutamatergic System in 5xFAD Mice.
Lee HJ, Kim HY, Oh SJ … +4 more , Son Y, Kang KJ, Nam KR, Choi JY
Mol Imaging Biol · 2024 Oct · PMID 39174788 · Publisher ↗
PURPOSE: Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic sy...
PURPOSE: Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic system in the brain is known to play an important role in memory and learning in the neural circuits. However, there has been limited research on how antipsychotic drugs affect the glutamatergic system of AD. Therefore, we aimed to investigate the effects of aripiprazole on the glutamatergic system in an animal model of AD using functional molecular imaging. PROCEDURES: In this study, 5xFAD mice were used as the animal model. At the age of 5 months, the mice were divided into wild-type, vehicle control, and aripiprazole-treated groups (n = 6 per group). The aripiprazole-treated group was administered aripiprazole for 2 months at a dose of 1 mg·kg·day. At 7 months of age, the animals underwent behavioral tests and glutamate positron emission tomography (PET) scans. RESULTS: The aripiprazole-treated group exhibited alleviated memory impairment in a novel object recognition test. Moreover, this group displayed 7-8% higher binding in the glutamate PET scan than the vehicle-treated 5xFAD group. Postmortem examination confirmed the recovery of glutamatergic damage. CONCLUSIONS: The administration of aripiprazole alleviated memory impairment and restored the damaged glutamatergic system in 5xFAD mice. Although the use of aripiprazole in AD patients may be a constraint in terms of safety, we confirmed the possibility that the administration of antipsychotic drugs can be effective in AD.
Application of Dynamic [F]FDG PET/CT Multiparametric Imaging Leads to an Improved Differentiation of Benign and Malignant Lung Lesions.
Zhao Y, Lv T, Xu Y … +7 more , Yin J, Wang X, Xue Y, Zhu G, Yu W, Wang H, Li X
Mol Imaging Biol · 2024 Oct · PMID 39174787 · Publisher ↗
PURPOSE: To evaluate the potential of whole-body dynamic (WBD) 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) multiparametric imaging in the differential diagnosis between...
PURPOSE: To evaluate the potential of whole-body dynamic (WBD) 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) multiparametric imaging in the differential diagnosis between benign and malignant lung lesions. PROCEDURES: We retrospectively analyzed WBD PET/CT scans from patients with lung lesions performed between April 2020 and March 2023. Multiparametric images including standardized uptake value (SUV), metabolic rate (MR) and distribution volume (DV) were visually interpreted and compared. We adopted SUV, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for semi-quantitative analysis, MR and DV values for quantitative analysis. We also collected the patients' clinical characteristics. The variables above with P-value < 0.05 in the univariate analysis were entered into a multivariate logistic regression. The statistically significant metrics were plotted on receiver-operating characteristic (ROC) curves. RESULTS: A total of 60 patients were included for data evaluation. We found that most malignant lesions showed high uptake on MR and SUV images, and low or absent uptake on DV images, while benign lesions showed low uptake on MR images and high uptake on DV images. Most malignant lesions showed a characteristic pattern of gradually increasing FDG uptake, whereas benign lesions presented an initial rise with rapid fall, then kept stable at a low level. The AUC values of MR and SUV are 0.874 (95% CI: 0.763-0.946) and 0.792 (95% CI: 0.667-0.886), respectively. DeLong's test showed the difference between the areas is statistically significant (P < 0.001). CONCLUSIONS: Our study demonstrated that dynamic [F]FDG PET/CT imaging based on the Patlak analysis was a more accurate method of distinguishing malignancies from benign lesions than conventional static PET/CT scans.
Comparison of the Accuracy of a Deep Learning Method for Lesion Detection in PET/CT and PET/MRI Images.
Pang L, Zhang Z, Liu G … +9 more , Hu P, Chen S, Gu Y, Huang Y, Zhang J, Shi Y, Cao T, Zhang Y, Shi H
Mol Imaging Biol · 2024 Oct · PMID 39141195 · Publisher ↗
PURPOSE: Develop a universal lesion recognition algorithm for PET/CT and PET/MRI, validate it, and explore factors affecting performance. PROCEDURES: The 2022 AutoPet Challenge's 1014 PET/CT dataset was used to train the...
PURPOSE: Develop a universal lesion recognition algorithm for PET/CT and PET/MRI, validate it, and explore factors affecting performance. PROCEDURES: The 2022 AutoPet Challenge's 1014 PET/CT dataset was used to train the lesion detection model based on 2D and 3D fractional-residual (F-Res) models. To extend this to PET/MRI, a network for converting MR images to synthetic CT (sCT) was developed, using 41 sets of whole-body MR and corresponding CT data. 38 patients' PET/CT and PET/MRI data were used to verify the universal lesion recognition algorithm. Image quality was assessed using signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Total lesion glycolysis (TLG), metabolic tumor volume (MTV), and lesion count were calculated from the resultant lesion masks. Experienced physicians reviewed and corrected the model's outputs, establishing the ground truth. The performance of the lesion detection deep-learning model on different PET images was assessed by detection accuracy, precision, recall, and dice coefficients. Data with a detection accuracy score (DAS) less than 1 was used for analysis of outliers. RESULTS: Compared to PET/CT, PET/MRI scans had a significantly longer delay time (135 ± 45 min vs 61 ± 12 min) and lower SNR (6.17 ± 1.11 vs 9.27 ± 2.77). However, CNR values were similar (7.37 ± 5.40 vs 5.86 ± 6.69). PET/MRI detected more lesions (with a mean difference of -3.184). TLG and MTV showed no significant differences between PET/CT and PET/MRI (TLG: 119.18 ± 203.15 vs 123.57 ± 151.58, p = 0.41; MTV: 36.58 ± 57.00 vs 39.16 ± 48.34, p = 0.33). A total of 12 PET/CT and 14 PET/MRI datasets were included in the analysis of outliers. Outlier analysis revealed PET/CT anomalies in intestines, ureters, and muscles, while PET/MRI anomalies were in intestines, testicles, and low tracer uptake regions, with false positives in ureters (PET/CT) and intestines/testicles (PET/MRI). CONCLUSION: The deep learning lesion detection model performs well with both PET/CT and PET/MRI. SNR, CNR and reconstruction parameters minimally impact recognition accuracy, but delay time post-injection is significant.
Correction to: Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers.
Leach BI, Lister D, Adams SR … +5 more , Bykowski J, Schwartz AB, McConville P, Dimant H, Ahrens ET
Mol Imaging Biol · 2024 Oct · PMID 39102171 · Publisher ↗
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Clinical Performance Comparison of a Long Versus a Short Axial Field-of-View PET/CT Using EARL-Compliant Reconstructions.
Roya M, van Snick JH, Slart RHJA … +7 more , Noordzij W, Stormezand GN, Willemsen ATM, Boellaard R, Glaudemans AWJM, Tsoumpas C, van Sluis J
Mol Imaging Biol · 2024 Oct · PMID 39093483 · Full text
PURPOSE: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required....
PURPOSE: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision. PROCEDURES: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[F]fluoro-D-glucose injection and underwent routine clinical ( 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test. RESULTS: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra. CONCLUSION: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations.
Investigation of the Impact of the H310A FcRn Region Mutation on Zr-Immuno-PET Brain Imaging with a BBB-Shuttle Anti‑Amyloid Beta Antibody.
Wuensche TE, Stergiou N, Mes I … +9 more , Verlaan M, Kooijman EJM, Windhorst AD, Jensen A, Asuni AA, Bang-Andersen B, van Dongen GAMS, Vugts DJ, Beaino W
Mol Imaging Biol · 2024 Oct · PMID 39093482 · Full text
PURPOSE: In the emerging field of antibody treatments for neurodegenerative diseases, reliable tools are needed to evaluate new therapeutics, diagnose and select patients, monitor disease progression, and assess therapy...
PURPOSE: In the emerging field of antibody treatments for neurodegenerative diseases, reliable tools are needed to evaluate new therapeutics, diagnose and select patients, monitor disease progression, and assess therapy response. Immuno-PET combines the high affinity and exceptional specificity of monoclonal antibodies with the non-invasive imaging technique positron emission tomography (PET). Its application in neurodegenerative disease brain imaging has been limited due to the marginal uptake across the blood-brain barrier (BBB). The emergence of BBB-shuttle antibodies with enhanced uptake across the BBB extended immuno-PET to brain imaging. We recently reported about specific brain uptake of a bispecific aducanumab mTfR antibody in APP/PS1 TG mice using Zr-immuno-PET. However, a sufficient target-to-background ratio was reached at a relatively late scanning time point of 7 days post-injection. To investigate if a better target-to-background ratio could be achieved earlier, an aducanumab BBB-shuttle with a mutated Fc region for reduced FcRn affinity was evaluated. PROCEDURES: Adu-8D3 and Adu-8D3 were modified with DFO*-NCS and subsequently radiolabeled with Zr. The potential influence of the H310A mutation, modification with DFO*-NCS, and subsequent radiolabeling on the in vitro binding to amyloid-beta and mTfR1 was investigated via amyloid-beta peptide ELISA and FACS analysis using mTfR1 transfected CHO-S cells. Blood kinetics, brain uptake, in vivo PET imaging and target engagement of radiolabeled Adu-8D3 were evaluated and compared to non-mutated Adu-8D3 in APP/PS1 TG mice and wild-type animals as controls. RESULTS: Radiolabeling was performed with sufficient radiochemical yields and radiochemical purity. In vitro binding to amyloid-beta and mTfR1 showed no impairment. [Zr]Zr-Adu-8D3 showed faster blood clearance and earlier differentiation of amyloid-beta-related brain uptake compared to [Zr]Zr-Adu-8D3. However, only half of the brain uptake was observed for [Zr]Zr-Adu-8D3. CONCLUSIONS: Although a faster blood clearance of Adu-8D3 was observed, it was concluded that no beneficial effects for Zr-immuno-PET imaging of brain uptake were obtained.
Interobserver Agreement Rates on CXCR4-Directed PET/CT in Patients with Marginal Zone Lymphoma.
Werner RA, Zhi Y, Dreher N … +11 more , Samnick S, Kosmala A, Higuchi T, Bundschuh L, Lapa C, Buck AK, Topp MS, Einsele H, Duell J, Serfling SE, Bundschuh RA
Mol Imaging Biol · 2024 Oct · PMID 39090381 · Full text
UNLABELLED: C-X-C motif chemokine receptor 4 (CXCR4)-directed molecular imaging provides excellent read-out capabilities in patients with marginal zone lymphoma (MZL). We aimed to determine the interobserver agreement ra...
UNLABELLED: C-X-C motif chemokine receptor 4 (CXCR4)-directed molecular imaging provides excellent read-out capabilities in patients with marginal zone lymphoma (MZL). We aimed to determine the interobserver agreement rate of CXCR4-targeted PET/CT among readers with different levels of experience. METHODS: 50 subjects with MZL underwent CXCR4-targeted PET/CT, which were reviewed by four readers (including two experienced and two less experienced observers). The following 8 parameters were investigated: overall scan result, CXCR4 density in lymphoma tissue, extranodal organ involvement, No. of affected extranodal organs and extranodal organ metastases, lymph node (LN) involvement and No. of affected LN areas and LN metastases. We applied intraclass correlation coefficients (ICC; < 0.4, poor; 0.4-0.59, fair; 0.6-0.74, good and > 0.74 excellent agreement rates). RESULTS: Among all readers, fair agreement was recorded for No. of affected extranodal organs (ICC, 0.40; 95% confidence interval [CI], 0.25-0.68), overall scan result (ICC, 0.42; 95%CI, 0.28-0.57), CXCR4 density in lymphoma tissue (ICC, 0.52; 95%CI, 0.38-0.66), and No. of extranodal organ metastases (ICC, 0.55; 95%CI, 0.41-0.61) and LN involvement (ICC, 0.59; 95%CI, 0.46-0.71). Good agreement rates were observed for No. of LN metastases (ICC, 0.71; 95%CI, 0.60-0.81) and No. of LN areas (ICC, 0.73; 95%CI, 0.63-0.82), while extranodal organ involvement (ICC, 0.35; 95%CI, 0.21-0.51) achieved poor concordance. On a reader-by-reader comparison, the experienced readers achieved significantly higher agreement rates in 4/8 (50%) investigated scan items (ICC, range, 0.21-0.90, P < / = 0.04). In the remaining 4/8 (50%), a similar trend with higher ICCs for the experienced readers was recorded (n.s.). CONCLUSION: CXCR4-directed PET/CT mainly provided fair to good agreement rates for scan assessment, while a relevant level of experience seems to be required for an accurate imaging read-out.
The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [F]FDG Imaging.
Novruzov E, Dabir M, Schmitt D … +10 more , Mattes-György K, Beu M, Mori Y, Antke C, Reinartz S, Lichtenberg A, Antoch G, Giesel FL, Aubin H, Mamlins E
Mol Imaging Biol · 2024 Oct · PMID 39085535 · Full text
PURPOSE: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy...
PURPOSE: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection. PROCEDURES: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard. RESULTS: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555-0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571-0.964), respectively. CONCLUSIONS: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.
Volume-Based Quantitative Measurement of [F]AlF-NOTA-FAPI-04 PET/CT Uptake Reflects the Disease Activity of IgG4-Related Disease.
Wan L, Sun C, Liang J … +2 more , Lin J, Chen Z
Mol Imaging Biol · 2024 Oct · PMID 39080158 · Full text
BACKGROUND: To investigate the potential utility of quantitative parameters obtained by F-fibroblast activation protein inhibitor positron emission tomography/computed tomography ([F]AlF-NOTA-FAPI-04 PET/CT) in the asses...
BACKGROUND: To investigate the potential utility of quantitative parameters obtained by F-fibroblast activation protein inhibitor positron emission tomography/computed tomography ([F]AlF-NOTA-FAPI-04 PET/CT) in the assessment of organ involvement and disease activity in IgG4-related disease (IgG4-RD). METHODS: This study enrolled patients who underwent [F]AlF-NOTA-FAPI-04 PET/CT scans at the Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine from August 2021 to August 2022. The PET/CT images of the included patients were re-evaluated by PET center technicians, and the maximal standardized uptake value (SUV), metabolic lesion volume (MLV), and total lesion FAPI (TL-FAPI) were used to evaluate the involved organs and tissues that abnormally accumulated [F]AlF-NOTA-FAPI-04. The clinical and laboratory data of patients are also systematically collected and analyzed. RESULTS: Among the patients included in this study, 12 patients met the IgG4-RD classification criteria established by the American College of Rheumatology in 2019. Among them, 8 were males and 4 were females, with an average age of 59.3 ± 11.5 years. 50% of IgG4-RD patients were found with more organ involvement on PET/CT than physical examination, ultrasonography, and computed tomography. IgG4 levels (Rho = 0.594, p = 0.042) and IgG4-RI (Rho = 0.647, p = 0.023) were significantly positively correlated with TL-FAPI. After linear regression analysis, only TL-FAPI showed a predictive value of RI (R = 0.356, B = 0.008, p = 0.041). CONCLUSIONS: [F]AlF-NOTA-FAPI-04 PET/CT is a useful tool for identifying asymptomatic organ involvement and assessing disease activity. The TL-FAPI as an indicator was positively correlated with IgG4-RD disease activity.
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