Morten Bentestuen MD , Noor Al-Obaydi MD , Helle D. Zacho MD, PhD, DMSc
{"title":"FAPI-avid nonmalignant PET/CT findings: An expedited systematic review","authors":"Morten Bentestuen MD , Noor Al-Obaydi MD , Helle D. Zacho MD, PhD, DMSc","doi":"10.1053/j.semnuclmed.2023.02.001","DOIUrl":"10.1053/j.semnuclmed.2023.02.001","url":null,"abstract":"<div><p>Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported.</p><p>A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with <sup>68</sup>Ga or <sup>18</sup>F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10355422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suresh Alati PhD , Rajan Singh PhD , Martin G. Pomper MD, PhD , Steven P. Rowe MD, PhD , Sangeeta Ray Banerjee PhD
{"title":"Preclinical Development in Radiopharmaceutical Therapy for Prostate Cancer","authors":"Suresh Alati PhD , Rajan Singh PhD , Martin G. Pomper MD, PhD , Steven P. Rowe MD, PhD , Sangeeta Ray Banerjee PhD","doi":"10.1053/j.semnuclmed.2023.06.007","DOIUrl":"10.1053/j.semnuclmed.2023.06.007","url":null,"abstract":"<div><p><span>Prostate cancer<span><span> is a leading cause of cancer death in men worldwide. Among the various treatment<span> options, radiopharmaceutical<span> therapy has shown notable success in metastatic, castration-resistant disease. Radiopharmaceutical therapy is a systemic approach that delivers cytotoxic radiation doses precisely to the malignant tumors and/or tumor microenvironment. Therapeutic radiopharmaceuticals are composed of a </span></span></span>therapeutic radionuclide<span> and a high-affinity, tumor-targeting carrier molecule. Therapeutic radionuclides used in preclinical prostate cancer studies are primarily α-, β</span></span></span><sup>−</sup><span><span><span>-, or Auger-electron-emitting radiometals or radiohalogens. Monoclonal antibodies, antibody-derived fragments, peptides, and small molecules are frequently used as tumor-targeting molecules. Over the years, several important membrane-associated </span>proteases and receptors have been identified, validated, and subsequently used for preclinical radiotherapeutic development for prostate cancer. Prostate-specific membrane antigen (PSMA) is the most well-studied prostate cancer-associated protease in preclinical literature. PSMA-targeting radiotherapeutic agents are being investigated using high-affinity antibody- and small-molecule-based agents for safety and efficacy. Early generations of such agents were developed simply by replacing radionuclides of the </span>imaging agents with therapeutic ones. Later, extensive structure-activity relationship studies were conducted to address the safety and efficacy issues obtained from initial patient data. Recent regulatory approval of the </span><sup>177</sup>Lu-labeled low-molecular-weight agent, <sup>177</sup>Lu-PSMA-617, is a significant accomplishment. Current preclinical experiments are focused on the structural modification of <sup>177</sup>Lu-PSMA-617 and relevant investigational agents to increase tumor targeting and reduce off-target binding and toxicity in healthy organs. While lutetium-177 (<sup>177</sup>Lu) remains the most widely used radionuclide, radiolabeled analogs with iodine-131 (<sup>128</sup>I), yttrium-90 (<sup>89</sup>Y), copper-67 (<sup>67</sup>Cu), and terbium-161 (<sup>161</sup>Tb) have been evaluated as potential alternatives in recent years. In addition, agents carrying the α-particle-emitting radiohalogen, astatine-211 (<sup>211</sup>At), or radiometals, actinium-225 (<sup>225</sup>Ac), lead-212 (<sup>212</sup>Pb), radium-223 (<sup>223</sup>Ra), and thorium-227 (<sup>227</sup><span><span><span>Th), have been increasingly investigated in preclinical research. Besides PSMA-based radiotherapeutics, other prominent prostate cancer-related proteases, for example, human kallikrein </span>peptidases<span> (HK2 and HK3), have been explored using monoclonal-antibody-(mAb)-based targeting platforms. Several promising mAbs targeting receptors overexpressed on the different stages of prostate cancer have a","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aage K.O. Alstrup DVM, PhD , Mie R. Dollerup , Mette I.T. Simonsen , Mikkel H. Vendelbo MD, PhD
{"title":"Preclinical Imaging Studies: Protocols, Preparation, Anesthesia, and Animal Care","authors":"Aage K.O. Alstrup DVM, PhD , Mie R. Dollerup , Mette I.T. Simonsen , Mikkel H. Vendelbo MD, PhD","doi":"10.1053/j.semnuclmed.2023.02.003","DOIUrl":"10.1053/j.semnuclmed.2023.02.003","url":null,"abstract":"<div><p><span>Today preclinical PET imaging connects laboratory research with clinical applications. Here PET clearly bridges the gap, as nearly identical imaging protocols can be applied to both animal and humans. However, some hurdles exist and researchers must be careful, partly because the animals are usually anesthetized during the scans, while human volunteers are awake. This review is based on our own experiences of some of the most important pitfalls and how to overcome them. This includes how studies should be designed, how to select the right anesthesia and monitoring. The choice of anesthesia is quite crucial, as it may have a greater influence on the results than the effect of the tested procedures. Monitoring is necessary, as the animals cannot fully maintain homeostasis during anesthesia, and reliable results are dependent on a stable physiology. Additionally, it is important to note that rodents, in particular, are prone to rapidly becoming hypothermic. Thus, the selection of an appropriate anesthetic and monitoring protocol is crucial for both obtaining accurate results and ensuring animal welfare. Prior to imaging, catheters for </span>tracer administration and, if necessary, blood sampling should be implanted. The administration of tracers should be done in a manner that minimizes interference with the scans, and the same applies to any serial blood sampling. The limited blood volume and organ size of rodents should also be taken into consideration when planning experiments. Finally, if the animal needs to be awakened after the scan, proper care must be taken to ensure their welfare.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janke Kleynhans PhD , Mike Machaba Sathekge MD, PhD , Thomas Ebenhan PhD
{"title":"Preclinical Research Highlighting Contemporary Targeting Mechanisms of Radiolabelled Compounds for PET Based Infection Imaging","authors":"Janke Kleynhans PhD , Mike Machaba Sathekge MD, PhD , Thomas Ebenhan PhD","doi":"10.1053/j.semnuclmed.2023.03.001","DOIUrl":"10.1053/j.semnuclmed.2023.03.001","url":null,"abstract":"<div><p>It is important to constantly monitor developments in the preclinical imaging arena of infection. Firstly, novel radiopharmaceuticals with the correct characteristics must be identified to funnel into the clinic. Secondly, it must be evaluated if enough innovative research is being done and adequate resources are geared towards the development of radiopharmaceuticals that could feed into the Nuclear Medicine Clinic in the near future. It is proposed that the ideal infection imaging agent will involve PET combined with CT but more ideally MRI. The radiopharmaceuticals currently presented in preclinical literature have a wide selection of vectors and targets. Ionic formulations of PET-radionuclides such <sup>64</sup>CuCl<sub>2</sub> and <sup>68</sup>GaCl<sub>2</sub> are evaluated for bacterial infection imaging. Many small molecule based radiopharmaceuticals are being investigated with the most prominent targets being cell wall synthesis, maltodextrin transport (such as [<sup>18</sup>F]F-maltotriose), siderophores (bacterial and fungal infections), the folate synthesis pathway (such as [<sup>18</sup>F]F-PABA) and protein synthesis (radiolabelled puromycin). Mycobacterial specific antibiotics, antifungals and antiviral agents are also under investigation as infection imaging agents. Peptide based radiopharmaceuticals are developed for bacterial, fungal and viral infections. The radiopharmaceutical development could even react quickly enough on a pandemic to develop a SARS-CoV-2 imaging agent in a timely fashion ([<sup>64</sup>Cu]Cu-NOTA-EK1). New immuno-PET agents for the imaging of viruses have recently been published, specifically for HIV persistence but also for SARS-CoV2. A very promising antifungal immuno-PET agent (hJ5F) is also considered. Future technologies could include the application of aptamers and bacteriophages and even going as far as the design of theranostic infection. Another possibility would be the application of nanobodies for immuno-PET applications. Standardization and optimization of the preclinical evaluation of radiopharmaceuticals could enhance clinical translation and reduce time spent in pursuing less than optimal candidates.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10347912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aage Kristian Olsen Alstrup DVM, PhD , Morten Busk PhD , Anita Dittrich MS , Kasper Hansen PhD , Tobias Wang PhD , Mads Damkjær PhD , Johnnie Bremholm Andersen PhD , Henrik Lauridsen PhD
{"title":"Special Challenges in PET Imaging of Ectothermic Vertebrates","authors":"Aage Kristian Olsen Alstrup DVM, PhD , Morten Busk PhD , Anita Dittrich MS , Kasper Hansen PhD , Tobias Wang PhD , Mads Damkjær PhD , Johnnie Bremholm Andersen PhD , Henrik Lauridsen PhD","doi":"10.1053/j.semnuclmed.2023.06.006","DOIUrl":"10.1053/j.semnuclmed.2023.06.006","url":null,"abstract":"<div><p>The bulk of biomedical positron emission tomography (PET)-scanning experiments are performed on mammals (ie, rodents, pigs, and dogs), and the technique is only infrequently applied to answer research questions in ectothermic vertebrates such as fish, amphibians, and reptiles. Nevertheless, many unique and interesting physiological characteristics in these ectothermic vertebrates could be addressed in detail through PET. The low metabolic rate of ectothermic animals, however, may compromise the validity of physiological and biochemical parameters derived from the images created by PET and other scanning modalities. Here, we review some of the considerations that should be taken into account when PET scanning fish, amphibians, and reptiles. We present specific results from our own experiments, many of which remain previously unpublished, and we draw on examples from the literature. We conclude that knowledge on the natural history and physiology of the species studied and an understanding of the limitations of the PET scanning techniques are necessary to avoid the design of faulty experiments and erroneous conclusions.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Morten Busk PhD , Steffen Sinning PhD , Aage K.O. Alstrup DVM, PhD, Dr.Vet.Sci , Ole L. Munk PhD , Mikkel H. Vendelbo MD, PhD
{"title":"Nuclear Medicine Preclinical Research: The Role of Cell Cultures","authors":"Morten Busk PhD , Steffen Sinning PhD , Aage K.O. Alstrup DVM, PhD, Dr.Vet.Sci , Ole L. Munk PhD , Mikkel H. Vendelbo MD, PhD","doi":"10.1053/j.semnuclmed.2023.04.007","DOIUrl":"10.1053/j.semnuclmed.2023.04.007","url":null,"abstract":"<div><p>Cell lines are essential in biomedical research due to their adaptability and precise simulation of physiological and pathophysiological conditions. Cell culture techniques have greatly advanced our understanding of biology in various fields and are widely regarded as a reliable and durable tool. Their diverse applications make them indispensable in scientific research. Radiation-emitting compounds are commonly used in cell culture research to investigate biological processes. Radiolabeled compounds are utilized to study cell function, metabolism, molecular markers, receptor density, drug binding and kinetics, as well as to analyze the direct interaction of radiotracers with target organ cells. This allows for the examination of normal physiology and disease states. The In Vitro system simplifies the study and filters out nonspecific signals from the In Vivo environment, leading to more specific results. Moreover, cell cultures offer ethical advantages when evaluating new tracers and drugs in preclinical studies. While cell experiments cannot entirely replace animal experiments, they reduce the need for live animals in experimentation.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colleen Olkowski BS , Bruna Fernandes PhD , Gary L. Griffiths PhD , Frank Lin MD , Peter L. Choyke MD
{"title":"Preclinical Imaging of Prostate Cancer","authors":"Colleen Olkowski BS , Bruna Fernandes PhD , Gary L. Griffiths PhD , Frank Lin MD , Peter L. Choyke MD","doi":"10.1053/j.semnuclmed.2023.02.002","DOIUrl":"10.1053/j.semnuclmed.2023.02.002","url":null,"abstract":"<div><p>Prostate cancer remains a major cause of mortality and morbidity, affecting millions of men, with a large percentage expected to develop the disease as they reach advanced ages. Treatment and management advances have been dramatic over the past 50 years or so, and one aspect of these improvements is reflected in the multiple advances in diagnostic imaging techniques. Much attention has been focused on molecular imaging techniques that offer high sensitivity and specificity and can now more accurately assess disease status and detect recurrence earlier. During development of molecular imaging probes, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) must be evaluated in preclinical models of the disease. If such agents are to be translated to the clinic, where patients undergoing these imaging modalities are injected with a molecular imaging probe, these agents must first be approved by the FDA and other regulatory agencies prior to their adoption in clinical practice. Scientists have worked assiduously to develop preclinical models of prostate cancer that are relevant to the human disease to enable testing of these probes and related targeted drugs. Challenges in developing reproducible and robust models of human disease in animals are beset with practical issues such as the lack of natural occurrence of prostate cancer in mature male animals, the difficulty of initiating disease in immune-competent animals and the sheer size differences between humans and conveniently smaller animals such as rodents. Thus, compromises in what is ideal and what can be achieved have had to be made. The workhorse of preclinical animal models has been, and remains, the investigation of human xenograft tumor models in athymic immunocompromised mice. Later models have used other immunocompromised models as they have been found and developed, including the use of directly derived patient tumor tissues, completely immunocompromised mice, orthotopic methods for inducing prostate cancer within the mouse prostate itself and metastatic models of advanced disease. These models have been developed in close parallel with advances in imaging agent chemistries, radionuclide developments, computer electronics advances, radiometric dosimetry, biotechnologies, organoid technologies, advances in in vitro diagnostics, and overall deeper understandings of disease initiation, development, immunology, and genetics. The combination of molecular models of prostatic disease with radiometric-based studies in small animals will always remain spatially limited due to the inherent resolution sensitivity limits of PET and SPECT decay processes, fundamentally set at around a 0.5 cm resolution limit. Nevertheless, it is central to researcher's efforts and to successful clinical translation that the best animal models are adopted, accepted, and scientifically verified as part of this truly interdisciplinary approach to addressing this important disea","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radium-223 for the Treatment of Painful Bone Metastates in Castration-resistant Prostate Cancer","authors":"Elif Özdemir","doi":"10.4274/nts.galenos.2023.0016","DOIUrl":"https://doi.org/10.4274/nts.galenos.2023.0016","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88476831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}