Pub Date : 2023-09-01DOI: 10.4274/nts.galenos.2023.0015
Gamze Beydağı, N. Alan Selçuk, L. Kabasakal
{"title":"Alpha Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors","authors":"Gamze Beydağı, N. Alan Selçuk, L. Kabasakal","doi":"10.4274/nts.galenos.2023.0015","DOIUrl":"https://doi.org/10.4274/nts.galenos.2023.0015","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":"87194367","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}
The development of novel PET imaging agents that selectively bind specific dementia-related targets can contribute significantly to accurate, differential and early diagnosis of dementia causing diseases and support the development of therapeutic agents. Consequently, in recent years there has been a growing body of literature describing the development and evaluation of potential new promising PET tracers for dementia. This review article provides a comprehensive overview of novel dementia PET probes under development, classified by their target, and pinpoints their preclinical evaluation pathway, typically involving in silico, in vitro and ex/in vivo evaluation. Specific target-associated challenges and pitfalls, requiring extensive and well-designed preclinical experimental evaluation assays to enable successful clinical translation and avoid shortcomings observed for previously developed ‘well-established’ dementia PET tracers are highlighted in this review.
{"title":"Preclinical Evaluation of Novel PET Probes for Dementia","authors":"Romy Cools MSc , Kobe Kerkhofs MSc , Renan C.F. Leitao PhD , Guy Bormans PhD","doi":"10.1053/j.semnuclmed.2023.03.004","DOIUrl":"10.1053/j.semnuclmed.2023.03.004","url":null,"abstract":"<div><p><span><span>The development of novel PET imaging agents that selectively bind specific dementia-related targets can contribute significantly to accurate, differential and early diagnosis of dementia causing </span>diseases<span> and support the development of therapeutic agents. Consequently, in recent years there has been a growing body of literature describing the development and evaluation of potential new promising PET tracers for dementia. This review article provides a comprehensive overview of novel dementia PET probes under development, classified by their target, and pinpoints their preclinical evaluation pathway, typically involving </span></span>in silico, in vitro and ex/in vivo evaluation. Specific target-associated challenges and pitfalls, requiring extensive and well-designed preclinical experimental evaluation assays to enable successful clinical translation and avoid shortcomings observed for previously developed ‘well-established’ dementia PET tracers are highlighted in this review.</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":"10030814","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}
Pub Date : 2023-09-01DOI: 10.4274/nts.galenos.2023.0014
N. Alan Selçuk, Kaan Akçay, L. Kabasakal
{"title":"The Role of Alpha Therapy in Metastatic Castration Resistance Prostate Cancer","authors":"N. Alan Selçuk, Kaan Akçay, L. Kabasakal","doi":"10.4274/nts.galenos.2023.0014","DOIUrl":"https://doi.org/10.4274/nts.galenos.2023.0014","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":"84279499","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}
Pub Date : 2023-09-01DOI: 10.4274/nts.galenos.2023.0013
Türkay Toklu
{"title":"Physical and Radiobiological Properties of Alpha Emitter Isotopes Used in Radionuclide Therapy","authors":"Türkay Toklu","doi":"10.4274/nts.galenos.2023.0013","DOIUrl":"https://doi.org/10.4274/nts.galenos.2023.0013","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":"73960244","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}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.04.008
Geoffrey M. Currie PhD
Academic integrity in both higher education and scientific writing has been challenged by developments in artificial intelligence. The limitations associated with algorithms have been largely overcome by the recently released ChatGPT; a chatbot powered by GPT-3.5 capable of producing accurate and human-like responses to questions in real-time. Despite the potential benefits, ChatGPT confronts significant limitations to its usefulness in nuclear medicine and radiology. Most notably, ChatGPT is prone to errors and fabrication of information which poses a risk to professionalism, ethics and integrity. These limitations simultaneously undermine the value of ChatGPT to the user by not producing outcomes at the expected standard. Nonetheless, there are a number of exciting applications of ChatGPT in nuclear medicine across education, clinical and research sectors. Assimilation of ChatGPT into practice requires redefining of norms, and re-engineering of information expectations.
{"title":"Academic integrity and artificial intelligence: is ChatGPT hype, hero or heresy?","authors":"Geoffrey M. Currie PhD","doi":"10.1053/j.semnuclmed.2023.04.008","DOIUrl":"10.1053/j.semnuclmed.2023.04.008","url":null,"abstract":"<div><p>Academic integrity in both higher education and scientific writing has been challenged by developments in artificial intelligence. The limitations associated with algorithms have been largely overcome by the recently released ChatGPT; a chatbot powered by GPT-3.5 capable of producing accurate and human-like responses to questions in real-time. Despite the potential benefits, ChatGPT confronts significant limitations to its usefulness in nuclear medicine and radiology. Most notably, ChatGPT is prone to errors and fabrication of information which poses a risk to professionalism, ethics and integrity. These limitations simultaneously undermine the value of ChatGPT to the user by not producing outcomes at the expected standard. Nonetheless, there are a number of exciting applications of ChatGPT in nuclear medicine across education, clinical and research sectors. Assimilation of ChatGPT into practice requires redefining of norms, and re-engineering of information expectations.</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":"9974030","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}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.04.004
Stephan G. Nekolla PhD , Christoph Rischpler MD , Takahiro Higuchi MD, PhD
Noninvasive imaging techniques, such as SPECT, PET, CT, echocardiography, or MRI, have become essential in cardiovascular research. They allow for the evaluation of biological processes in vivo without the need for invasive procedures. Nuclear imaging methods, such as SPECT and PET, offer numerous advantages, including high sensitivity, reliable quantification, and the potential for serial imaging. Modern SPECT and PET imaging systems, equipped with CT and MRI components in order to get access to morphological information with high spatial resolution, are capable of imaging a wide range of established and innovative agents in both preclinical and clinical settings. This review highlights the utility of SPECT and PET imaging as powerful tools for translational research in cardiology. By incorporating these techniques into a well-defined workflow- similar to those used in clinical imaging- the concept of “bench to bedside” can be effectively implemented.
{"title":"Preclinical Imaging of Cardiovascular Disesase","authors":"Stephan G. Nekolla PhD , Christoph Rischpler MD , Takahiro Higuchi MD, PhD","doi":"10.1053/j.semnuclmed.2023.04.004","DOIUrl":"10.1053/j.semnuclmed.2023.04.004","url":null,"abstract":"<div><p><span><span><span>Noninvasive imaging techniques, such as </span>SPECT, </span>PET<span>, CT, echocardiography<span>, or MRI, have become essential in cardiovascular research. They allow for the evaluation of biological processes in vivo without the need for invasive procedures. </span></span></span>Nuclear imaging<span><span> methods, such as SPECT and PET, offer numerous advantages, including high sensitivity, reliable quantification, and the potential for serial imaging. Modern SPECT and PET imaging systems, equipped with CT and MRI components in order to get access to morphological information with high spatial resolution, are capable of imaging a wide range of established and innovative agents in both preclinical and clinical settings. This review highlights the utility of SPECT and PET imaging as powerful tools for translational research in </span>cardiology. By incorporating these techniques into a well-defined workflow- similar to those used in clinical imaging- the concept of “bench to bedside” can be effectively implemented.</span></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":"10030832","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}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.02.001
Morten Bentestuen MD , Noor Al-Obaydi MD , Helle D. Zacho MD, PhD, DMSc
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.
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 68Ga or 18F 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.
{"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}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.06.007
Suresh Alati PhD , Rajan Singh PhD , Martin G. Pomper MD, PhD , Steven P. Rowe MD, PhD , Sangeeta Ray Banerjee PhD
Prostate cancer is a leading cause of cancer death in men worldwide. Among the various treatment options, radiopharmaceutical 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 therapeutic radionuclide and a high-affinity, tumor-targeting carrier molecule. Therapeutic radionuclides used in preclinical prostate cancer studies are primarily α-, β−-, 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 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 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 177Lu-labeled low-molecular-weight agent, 177Lu-PSMA-617, is a significant accomplishment. Current preclinical experiments are focused on the structural modification of 177Lu-PSMA-617 and relevant investigational agents to increase tumor targeting and reduce off-target binding and toxicity in healthy organs. While lutetium-177 (177Lu) remains the most widely used radionuclide, radiolabeled analogs with iodine-131 (128I), yttrium-90 (89Y), copper-67 (67Cu), and terbium-161 (161Tb) have been evaluated as potential alternatives in recent years. In addition, agents carrying the α-particle-emitting radiohalogen, astatine-211 (211At), or radiometals, actinium-225 (225Ac), lead-212 (212Pb), radium-223 (223Ra), and thorium-227 (227Th), have been increasingly investigated in preclinical research. Besides PSMA-based radiotherapeutics, other prominent prostate cancer-related proteases, for example, human kallikrein peptidases (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
{"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}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.02.003
Aage K.O. Alstrup DVM, PhD , Mie R. Dollerup , Mette I.T. Simonsen , Mikkel H. Vendelbo MD, PhD
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 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.
{"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}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.03.001
Janke Kleynhans PhD , Mike Machaba Sathekge MD, PhD , Thomas Ebenhan PhD
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 64CuCl2 and 68GaCl2 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 [18F]F-maltotriose), siderophores (bacterial and fungal infections), the folate synthesis pathway (such as [18F]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 ([64Cu]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.
{"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}