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Series of myocardial FDG uptake requiring considerations of myocardial abnormalities in FDG-PET/CT.
Minamimoto, R
Japanese journal of radiology. 2021;(6):540-557
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Abstract
Distinct from cardiac PET performed with preparation to control physiological FDG uptake in the myocardium, standard FDG-PET/CT performed with 4-6 h of fasting will show variation in myocardial FDG uptake. For this reason, important signs of myocardial and pericardial abnormality revealed by myocardial FDG uptake tend to be overlooked. However, recognition of possible underlying disease will support further patient management to avoid complications due to the disease. This review demonstrates the mechanism of FDG uptake in the myocardium, discusses the factors affecting uptake, and provides notable image findings that may suggest underlying disease.
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Radiotracers for Bone Marrow Infection Imaging.
Jødal, L, Afzelius, P, Alstrup, AKO, Jensen, SB
Molecules (Basel, Switzerland). 2021;(11)
Abstract
INTRODUCTION Radiotracers are widely used in medical imaging, using techniques of gamma-camera imaging (scintigraphy and SPECT) or positron emission tomography (PET). In bone marrow infection, there is no single routine test available that can detect infection with sufficiently high diagnostic accuracy. Here, we review radiotracers used for imaging of bone marrow infection, also known as osteomyelitis, with a focus on why these molecules are relevant for the task, based on their physiological uptake mechanisms. The review comprises [67Ga]Ga-citrate, radiolabelled leukocytes, radiolabelled nanocolloids (bone marrow) and radiolabelled phosphonates (bone structure), and [18F]FDG as established radiotracers for bone marrow infection imaging. Tracers that are under development or testing for this purpose include [68Ga]Ga-citrate, [18F]FDG, [18F]FDS and other non-glucose sugar analogues, [15O]water, [11C]methionine, [11C]donepezil, [99mTc]Tc-IL-8, [68Ga]Ga-Siglec-9, phage-display selected peptides, and the antimicrobial peptide [99mTc]Tc-UBI29-41 or [68Ga]Ga-NOTA-UBI29-41. CONCLUSION Molecular radiotracers allow studies of physiological processes such as infection. None of the reviewed molecules are ideal for the imaging of infections, whether bone marrow or otherwise, but each can give information about a separate aspect such as physiology or biochemistry. Knowledge of uptake mechanisms, pitfalls, and challenges is useful in both the use and development of medically relevant radioactive tracers.
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Ramatroban-Based Analogues Containing Fluorine Group as Potential 18F-Labeled Positron Emission Tomography (PET) G-Protein Coupled Receptor 44 (GPR44) Tracers.
Huang, LA, Huang, KX, Tu, J, Kandeel, F, Li, J
Molecules (Basel, Switzerland). 2021;(5)
Abstract
Diabetes remains one of the fastest growing chronic diseases and is a leading source of morbidity and accelerated mortality in the world. Loss of beta cell mass (BCM) and decreased sensitivity to insulin underlie diabetes pathogenesis. Yet, the ability to safely and directly assess BCM in individuals with diabetes does not exist. Measures such as blood glucose provide only a crude indirect picture of beta cell health. PET imaging could, in theory, allow for safe, direct, and precise characterization of BCM. However, identification of beta cell-specific radiolabeled tracers remains elusive. G-protein coupled receptor 44 (GPR44) is a transmembrane protein that was characterized in 2012 as highly beta cell-specific within the insulin-positive islets of Langerhans. Accordingly, radiolabeling of existing GPR44 antagonists could be a viable method to accelerate PET tracer development. The present study aims to evaluate and summarize published analogues of the GPR44 antagonist ramatroban to develop 18F-labeled PET tracers for BCM analysis. The 77 corresponding ramatroban analogues containing a fluorine nuclide were characterized for properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile, and 32 compounds with favorable properties were identified. This review illustrates the potential of GPR44 analogues for the development of PET tracers.
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High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.
Jha, A, Taïeb, D, Carrasquillo, JA, Pryma, DA, Patel, M, Millo, C, de Herder, WW, Del Rivero, J, Crona, J, Shulkin, BL, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(11):2989-2995
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Abstract
Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
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Diagnostic Performance of PET or PET/CT with Different Radiotracers in Patients with Suspicious Lung Cancer or Pleural Tumours according to Published Meta-Analyses.
Lococo, F, Muoio, B, Chiappetta, M, Nachira, D, Petracca Ciavarella, L, Margaritora, S, Treglia, G
Contrast media & molecular imaging. 2020;:5282698
Abstract
PURPOSE Several meta-analyses have reported data about the diagnostic performance of positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) with different radiotracers in patients with suspicious lung cancer (LC) or pleural tumours (PT). This review article aims at providing an overview on the recent evidence-based data in this setting. METHODS A comprehensive literature search of meta-analyses published in PubMed/MEDLINE and Cochrane Library database from January 2010 through March 2020 about the diagnostic performance of PET or PET/CT with different radiotracers in patients with suspicious LC or PT was performed. This combination of keywords was used: (A) "PET" OR "positron emission tomography" AND (B) "lung" OR "pulmonary" OR "pleur∗" AND (C) meta-analysis. Only meta-analyses on PET or PET/CT in patients with suspicious LC or PT were selected. RESULTS We have summarized the diagnostic performance of PET or PET/CT with fluorine-18 fluorodeoxyglucose (18F-FDG) and other radiotracers taking into account 17 meta-analyses. Evidence-based data demonstrated a good diagnostic performance of 18F-FDG PET or PET/CT for the characterization of solitary pulmonary nodules (SPNs) or pleural lesions with overall higher sensitivity than specificity. Evidence-based data do not support the routine use of dual time point (DTP) 18F-FDG PET/CT or fluorine-18 fluorothymidine (18F-FLT) PET/CT in the differential diagnosis of SPNs. Even if 18F-FDG PET/CT has high sensitivity and specificity as a selective screening modality for LC, its role in this setting remains unknown. CONCLUSIONS Evidence-based data about the diagnostic performance of PET/CT with different radiotracers for suspicious LC or PT are increasing, with good diagnostic performance of 18F-FDG PET/CT. More prospective multicenter studies and cost-effectiveness analyses are warranted.
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18F-Sodium Fluoride PET: History, Technical Feasibility, Mechanism of Action, Normal Biodistribution, and Diagnostic Performance in Bone Metastasis Detection Compared with Other Imaging Modalities.
Ahuja, K, Sotoudeh, H, Galgano, SJ, Singh, R, Gupta, N, Gaddamanugu, S, Choudhary, G
Journal of nuclear medicine technology. 2020;(1):9-16
Abstract
The skeleton is the third most common site for metastasis overall, after the lungs and liver. Accurate diagnosis of osseous metastasis is critical for initial staging, treatment planning, restaging, treatment monitoring, and survival prediction. Currently, 99mTc-methylene diphosphonate whole-body scanning is the cornerstone of imaging to detect osseous metastasis. Although 18F-sodium fluoride (18F-NaF) was one of the oldest medical tracers for this purpose, it was replaced by other tracers because of their better physical properties, until recently. Continued development of PET scanners has opened a new era for 18F-NaF, and given its higher sensitivity, there have been increasing applications in imaging. In this review, we will discuss the history, technical aspects, radiobiology, and biodistribution of this tracer. Finally, we compare the accuracy of 18F-NaF PET with other conventional imaging methods for detection of osseous metastasis.
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Copper-64-immunoPET imaging: bench to bedside.
Natarajan, A
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2020;(4):356-363
Abstract
Positron emission tomography (PET) is a growing non-invasive diagnostic and molecular imaging tool in nuclear medicine, that is used to identify several diseases including cancer. The immunoPET probe is made up of monoclonal antibodies (mAbs) or its fragments or similar molecules that tagged with positron radioisotopes (68Ga, 64Cu, 89Zr) bound together by a bifunctional chelator (BFC). This probe is designed to identify a specific disease. Currently, several immunoPET probes are being developed for preclinical as well as for clinical applications. These studies are showing promising results, both in preclinical and patients, using mostly 64Cu, 89Zr isotopes. This review elucidates the 64Cu based immunoPET applications, their pipelines and the emerging scope of this technique within the nuclear medicine and molecular imaging clinics from bench to bedside. Recently, immunoPET research have sharply increased especially after a big surge in approval of oncology antibodies by the FDA for immune checkpoint-blockade cancer immunotherapies. Currently, preclinical to clinical translations of immunoPET has several challenges, including designing probes, choice of radioisotopes, selection of stable BFC, and size of antibody and its tracer kinetics. All these obstacles will be addressed eventually by improving PET scanner sensitivity, designing appropriate size of imaging probe, and combining immunoPET with specific targeting antibodies. These improvements should contribute to the immunoPET becoming more applicable in clinics, which, in turn, will provide critical information for correct patient selection, for right dosing, and for the right time/staging of treatment.
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Alternative and New Radiopharmaceutical Agents for Lung Cancer.
Telo, S, Calderoni, L, Vichi, S, Zagni, F, Castellucci, P, Fanti, S
Current radiopharmaceuticals. 2020;(3):185-194
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Abstract
BACKGROUND FDG PET/CT imaging has an established role in lung cancer (LC) management. Whilst it is a sensitive technique, FDG PET/CT has a limited specificity in the differentiation between LC and benign conditions and is not capable of defining LC heterogeneity since FDG uptake varies between histotypes. OBJECTIVE To get an overview of new radiopharmaceuticals for the study of cancer biology features beyond glucose metabolism in LC. METHODS A comprehensive literature review of PubMed/Medline was performed using a combination of the following keywords: "positron emission tomography", "lung neoplasms", "non-FDG", "radiopharmaceuticals", "tracers". RESULTS Evidences suggest that proliferation markers, such as 18F-Fluorothymidine and 11CMethionine, improve LC staging and are useful in evaluating treatment response and progression free survival. 68Ga-DOTA-peptides are already routinely used in pulmonary neuroendocrine neoplasms (NENs) management and should be firstly performed in suspected NENs. 18F-Fluoromisonidazole and other radiopharmaceuticals show a promising impact on staging, prognosis assessment and therapy response in LC patients, by visualizing hypoxia and perfusion. Radiolabeled RGD-peptides, targeting angiogenesis, may have a role in LC staging, treatment outcome and therapy. PET radiopharmaceuticals tracing a specific oncogene/signal pathway, such as EGFR or ALK, are gaining interest especially for therapeutic implications. Other PET tracers, like 68Ga-PSMA-peptides or radiolabeled FAPIs, need more development in LC, though, they are promising for therapy purposes. CONCLUSION To date, the employment of most of the described tracers is limited to the experimental field, however, research development may offer innovative opportunities to improve LC staging, characterization, stratification and response assessment in an era of increased personalized therapy.
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Pigmented villous nodular synovitis mimicking metastases on 18F-FDG PET/CT in a patient with rectal mucosal melanoma: a case report.
Yen, YA, Wu, LC, Lu, NM, Lee, CH
BMC musculoskeletal disorders. 2020;(1):13
Abstract
BACKGROUND Mucosal melanomas are rare and have a high potential for metastasizing. Surgical resection is the treatment of choice for single distant metastases. Malignant melanoma usually shows the highest uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). 18F- FDG positron emission tomography /computed tomography (PET/CT) is usually used for melanoma staging. An extensive literature review revealed only 4 published case reports and an original paper involving 8 cases (12 cases in total) of patients with skin melanomas in whom pigmented villous nodular synovitis (PVNS) mimicked metastatic melanoma, however, none of the melanomas reported were of rectal mucosal origin. CASE PRESENTATION A 60-year-old woman presented with recent diagnosis of rectal mucosal melanoma, two additional 18F-FDG-avid lesions in the left ankle and left foot were detected on 18F-FDG PET/CT. Metastases were initially suspected; however, the final diagnosis was PVNS. CONCLUSIONS This is the first report of PVNS mimicking metastases on 18F-FDG PET/CT in a patient with rectal mucosal melanoma. Although high 18F-FDG-avid lesions in patients with rectal mucosal melanoma are highly suspected to be metastasis and warrant an meticulous examination, the present case is a reminder that in such patients, not all lesions with high 18F-FDG uptake, especially those near a joint, are metastases and that more extensive resection is unnecessary.
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The Impact of Emerging Bioconjugation Chemistries on Radiopharmaceuticals.
Fay, R, Holland, JP
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(5):587-591
Abstract
The use of radiolabeled antibodies, immunoglobulin fragments, and other proteins are an increasingly important sector of research for diagnostic imaging and targeted radiotherapy in nuclear medicine. As with all radiopharmaceuticals, efficient radiochemistry is a prerequisite to clinical translation. For proteins, variations in the primary amino acid sequence, the secondary structures, and tertiary folds, as well as differences in the size, charge, polarity, lipophilicity, and the presence of posttranslational modifications, add complexity to the system. The choice of radionuclide or chelate, and its impact on the thermodynamic, kinetic, and metabolic stability of a radiotracer, has attracted much attention but the chemistry by which the radionuclide is conjugated to the protein scaffold is of equal importance. Recently, a wealth of creative advances in protein ligation methods based on chemical, photochemical, and enzyme-mediated processes has emerged. As radiochemists explore alternative bioconjugation strategies, this article considers their potential impact on radiotracer design.