Global collaboration is the cornerstone of scientific advancement. Frontiers in Medicine has organized a series of special edition Research Topics, with the goal of highlighting the latest advancements in Nuclear Medicine across the globe, showcasing the academic excellence and high-quality work of internationally recognized researchers. These collections aim to shed light on the recent progress made across the entire breadth of the Nuclear Medicine field, and reflect on the future challenges faced by researchers across borders.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH)

The Johns Hopkins Hospital, Johns Hopkins Medicine

Frontiers in Medicine

Nuclear Medicine

Global Excellence in Nuclear Medicine: North America

In this editorial, the significance of global cooperation in promoting scientific knowledge, particularly in the field of Nuclear Medicine, is discussed. Frontiers in Medicine has arranged a special edition that features the work of distinguished researchers from North America and showcases their recent innovations in Nuclear Medicine.Effective communication of findings is a critical aspect of scientific progress, especially when it comes to patient care. The imaging report plays a vital role in this communication process. In their review, <a href="https://doi.org/10.3389/fmed.2022.1051309">Murad et al.</a> highlighted the need for standardized classification schemes and reporting guidelines for PET/CT scans using 18F-FDG, 68Ga-DOTA-peptides, and PSMA-based radiopharmaceuticals in oncology. These schemes ensure that imaging reports are clear, concise, and evidence-based, which makes clinical decision-making easier. The paper discusses various classification schemes for interpreting and reporting PET imaging for lymphoma, multiple myeloma, melanoma, head and neck cancers, prostate cancer, and neuroendocrine tumors. The review also mentions the novel PET Response Evaluation Criteria for Immunotherapy (PERCIMT). However, the authors caution that the implementation of these recently proposed interpretation schemes to new indications would require validation in further prospective studies before they can be integrated into routine clinical practice.Two articles in this series analyze the issue of diagnostic radiopharmaceutical extravasations during nuclear medicine procedures (<a href="https://doi.org/10.3389/fmed.2021.684157">Osborne et al.</a>; <a href="https://doi.org/10.3389/fmed.2021.728542">Crowley et al.</a>). The review article by <a href="https://doi.org/10.3389/fmed.2021.684157">Osborne et al.</a> challenges the long-standing assumptions regarding diagnostic radiopharmaceutical extravasations. According to the article, significant extravasations can harm patients and irradiate tissue beyond acceptable limits. The findings are based on a review of 58 peer-reviewed documents that suggest patient harm due to extravasation and evaluation of five extravasated patients who underwent repeat imaging at the authors' institutions. The study challenges the belief that diagnostic extravasations do not cause harm and emphasizes the need for monitoring and dosimetry of extravasated tissue in some cases. The study also recommends process improvements to reduce the frequency of extravasations in nuclear medicine procedures. This is important because quantification is essential in precision medicine, and we need to follow ALARA principles. The case report by <a href="https://doi.org/10.3389/fmed.2021.728542">Crowley et al.</a> highlights the importance of detecting the excess presence of the radiopharmaceutical 99mTc-MDP near the injection site during nuclear medicine procedures. Detecting extravasations or venous stasis early in the injection process is crucial for ensuring good quality of images and minimizing radiation dose to surrounding tissue. This case emphasizes the need for proactive measures to mitigate potential issues during radiopharmaceutical administration. Early detection of the excess presence of 99mTc-MDP near the injection site enables technologists to apply mitigation tactics early in the process. Detecting extravasation or stasis early in the injection process can be necessary for image interpretation and minimizing radiation dose to tissue.<a href="https://doi.org/10.3389/fmed.2023.1091463">Kim et al.</a> conducted a study to evaluate cerebrovascular malformations with the help of PET/MRI scan and a radiotracer flutriciclamide ([18F]GE-180). The study aimed to examine the role of neuroinflammation in cerebral cavernous malformations (CCM), investigate the uptake of flutriciclamide in different brain regions in CCM patients (n = 5) and controls (n = 6), and compare the uptake with iron deposition assessed by quantitative susceptibility mapping (QSM). The study concluded that the uptake of flutriciclamide in CCM lesions is positively correlated with QSM. Therefore, flutriciclamide can be used as a potential marker for neuroinflammation in CCM patients. Flutriciclamide uptake combined with QSM offers complementary information for lesion delineation. It highlights the benefits of hybrid modalities like PET/MRI that can not only locate CCM lesions but also quantify both neuroinflammation and iron deposition simultaneously.Collaboration on a global scale is critical for advancing scientific knowledge, particularly in the field of nuclear medicine. International researchers play a vital role in contributing to this field. Effective communication in patient care relies on standardized reporting guidelines. The literature continues to feature publications that demonstrate these ongoing efforts (<a href="#B1">1</a>–<a href="#B3">3</a>). Detecting and addressing extravasations during procedures is essential to prevent harm to patients and exceeding radiation limits. Radiopharmaceutical research, such as flutriciclamide, shows promise for a better understanding of diseases like CCM, and the optimization of simultaneous PET/MRI in performing multiparametric evaluation in oncology, specifically in brain, head and neck, breast, liver, colorectal, gynecologic, prostate, and bladder tumors, particularly in the pediatric population (<a href="#B4">4</a>–<a href="#B24">24</a>). Leading societies in nuclear medicine (SNMMI and EANM) and MRI (ISMRM) have released a consensus recommendation for PET/MRI in oncology (<a href="#B25">25</a>), as well as recently, SNMMI, ACNM, and ASNC released a joint position statement on extravasations of diagnostic radiopharmaceuticals and medical event reporting (<a href="#B26">26</a>). They summarized that the extravasations are best managed on an institutional level and do not require any additional NRC regulation. These extravasations do not cause issues in patient-safety but rather a quality-control issue as they may affect quality of diagnostic images, especially for quantitative studies. These indicate ongoing efforts to enhance the quality and safety of Nuclear Medicine practices through research and collaboration.AJ: Writing&#x2014;original draft, Writing&#x2014;review and editing. AC: Writing&#x2014;review and editing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.This work was done as part of the AJ&apos;s official duties as an NIH employee and is a Work of the United States Government.

Editorial: Global excellence in nuclear medicine: North America

AimNeuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous malformations (CCM). Flutriciclamide ([18F]GE-180) is a translocator protein (TSPO) targeting positron emission tomography (PET) tracer, developed for imaging neuroinflammation. The objectives of this study were to describe characteristics of flutriciclamide uptake in different brain tissue regions in CCM patients compared to controls, and to evaluate flutriciclamide uptake and iron deposition within CCM lesions.</sec>Materials and methodsFive patients with CCM and six controls underwent a 60 or 90 min continuous PET/MRI scan following 315 ± 68.9 MBq flutriciclamide administration. Standardized uptake value (SUV) and standardized uptake value ratio (SUVr) were obtained using the striatum as a pseudo-reference. Quantitative susceptibility maps (QSM) were used to define the location of the vascular malformation and calculate the amount of iron deposition in each lesion.</sec>ResultsIncreased flutriciclamide uptake was observed in all CCM lesions. The temporal pole demonstrated the highest radiotracer uptake; the paracentral lobule, cuneus and hippocampus exhibited moderate uptake; while the striatum had the lowest uptake, with average SUVs of 0.66, 0.55, 0.63, 0.55, and 0.33 for patient with CCM and 0.57, 0.50, 0.48, 0.42, and 0.32 for controls, respectively. Regional SUVr showed similar trends. The average SUV and QSM values in CCM lesions were 0.58 ± 0.23 g/ml and 0.30 ± 0.10 ppm. SUVs and QSM were positively correlated in CCM lesions (r = 0.53, p = 0.03).</sec>ConclusionThe distribution of flutriciclamide ([18F]GE-180) in the human brain and CCM lesions demonstrated the potential of this TSPO PET tracer as a marker of neuroinflammation that may be relevant for characterizing CCM disease progression along with QSM.</sec>

Aim: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous malformations (CCM). Flutriciclamide ([18F]GE-180) is a translocator protein (TSPO) targeting positron emission tomography (PET) tracer, developed for imaging neuroinflammation. The objectives of this study were to describe characteristics of flutriciclamide uptake in different brain tissue regions in CCM patients compared to controls, and to evaluate flutriciclamide uptake and iron deposition within CCM lesions.Materials and methods: Five patients with CCM and six controls underwent a 60 or 90 min continuous PET/MRI scan following 315 ± 68.9 MBq flutriciclamide administration. Standardized uptake value (SUV) and standardized uptake value ratio (SUVr) were obtained using the striatum as a pseudo-reference. Quantitative susceptibility maps (QSM) were used to define the location of the vascular malformation and calculate the amount of iron deposition in each lesion.Results: Increased flutriciclamide uptake was observed in all CCM lesions. The temporal pole demonstrated the highest radiotracer uptake; the paracentral lobule, cuneus and hippocampus exhibited moderate uptake; while the striatum had the lowest uptake, with average SUVs of 0.66, 0.55, 0.63, 0.55, and 0.33 for patient with CCM and 0.57, 0.50, 0.48, 0.42, and 0.32 for controls, respectively. Regional SUVr showed similar trends. The average SUV and QSM values in CCM lesions were 0.58 ± 0.23 g/ml and 0.30 ± 0.10 ppm. SUVs and QSM were positively correlated in CCM lesions (r = 0.53, p = 0.03).Conclusion: The distribution of flutriciclamide ([18F]GE-180) in the human brain and CCM lesions demonstrated the potential of this TSPO PET tracer as a marker of neuroinflammation that may be relevant for characterizing CCM disease progression along with QSM.

A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([18F]GE-180) PET/MRI

The imaging report is essential for the communication between physicians in patient care. The information it contains must be clear, concise with evidence-based conclusions and sufficient to support clinical decision-making. In recent years, several classification schemes and/or reporting guidelines for PET have been introduced. In this manuscript, we will review the classifications most frequently used in oncology for interpreting and reporting 18F-FDG PET imaging in lymphoma, multiple myeloma, melanoma and head and neck cancers, PSMA-ligand PET imaging for prostate cancer, and 68Ga-DOTA-peptide PET in neuroendocrine tumors (NET).

The imaging report is essential for the communication between physicians in patient care. The information it contains must be clear, concise with evidence-based conclusions and sufficient to support clinical decision-making. In recent years, several classification schemes and/or reporting guidelines for PET have been introduced. In this manuscript, we will review the classifications most frequently used in oncology for interpreting and reporting 18F-FDG PET imaging in lymphoma, multiple myeloma, melanoma and head and neck cancers, PSMA-ligand PET imaging for prostate cancer, and 68Ga-DOTA-peptide PET in neuroendocrine tumors (NET).

Standardized classification schemes in reporting oncologic PET/CT

Nuclear medicine extravasations and prolonged venous stasis may cause poor quality and quantification errors that can affect image interpretation and patient management. Radiopharmaceutical remaining near the administration site means that some portion of the radioactivity is not circulating as required for the prescribed uptake period. This case describes how detection of excess presence of 99mTc-MDP near the injection site enabled the technologist to apply mitigation tactics early in the uptake process. It also suggests that detecting an extravasation or stasis early in the injection process can be important for image interpretation and minimizing radiation dose to tissue.

Nuclear medicine extravasations and prolonged venous stasis may cause poor quality and quantification errors that can affect image interpretation and patient management. Radiopharmaceutical remaining near the administration site means that some portion of the radioactivity is not circulating as required for the prescribed uptake period. This case describes how detection of excess presence of 99mTc-MDP near the injection site enabled the technologist to apply mitigation tactics early in the uptake process. It also suggests that detecting an extravasation or stasis early in the injection process can be important for image interpretation and minimizing radiation dose to tissue.

Detection of Excess Presence of 99mTc-MDP Near Injection Site—A Case Report

Background: The patient benefit from a diagnostic nuclear medicine procedure far outweighs the associated radiation risk. This benefit/risk ratio assumes a properly administered radiopharmaceutical. However, a significant diagnostic radiopharmaceutical extravasation can confound the procedure in many ways. We identified three current extravasation hypotheses espoused by medical societies, advisory committees, and hundreds of individual members of the nuclear medicine community: diagnostic extravasations do not cause harm, do not result in high absorbed dose to tissue, and require complex dosimetry methods that are not readily available in nuclear medicine centers. We tested these hypotheses against a framework of current knowledge, recent developments, and original research. We conducted a literature review, searched regulatory databases, examined five clinical cases of extravasated patients, and performed dosimetry on those extravasations to test these globally accepted hypotheses.Results: A literature review found 58 peer-reviewed documents suggesting patient harm. Adverse event/vigilance report database reviews for extravasations were conducted and revealed 38 adverse events which listed diagnostic radiopharmaceutical extravasation as a factor, despite a regulatory exemption for required reporting. In our own case material, assessment of care was evaluated for five extravasated patients who underwent repeat imaging. Findings reflected results of literature review and included mis- or non-identification of lesions, underestimation of Standardized Uptake Values (SUVs) by 19–73%, classification of scans as non-diagnostic, and the need to repeat imaging with the associated additional radiation exposure, inconvenience, or delays in care. Dosimetry was performed for the same five cases of diagnostic radiopharmaceutical extravasation. Absorbed doses to 5 cm3 of tissue were between 1.1 and 8.7 Gy, and shallow dose equivalent for 10 cm2 of skin was as high as 4.2 Sv.Conclusions: Our findings suggest that significant extravasations can or have caused patient harm and can irradiate patients' tissue with doses that exceed medical event reporting limits and deterministic effect thresholds. Therefore, diagnostic radiopharmaceutical injections should be monitored, and dosimetry of extravasated tissue should be performed in certain cases where thresholds are thought to have been exceeded. Process improvement efforts should be implemented to reduce the frequency of extravasation in nuclear medicine.

Background: The patient benefit from a diagnostic nuclear medicine procedure far outweighs the associated radiation risk. This benefit/risk ratio assumes a properly administered radiopharmaceutical. However, a significant diagnostic radiopharmaceutical extravasation can confound the procedure in many ways. We identified three current extravasation hypotheses espoused by medical societies, advisory committees, and hundreds of individual members of the nuclear medicine community: diagnostic extravasations do not cause harm, do not result in high absorbed dose to tissue, and require complex dosimetry methods that are not readily available in nuclear medicine centers. We tested these hypotheses against a framework of current knowledge, recent developments, and original research. We conducted a literature review, searched regulatory databases, examined five clinical cases of extravasated patients, and performed dosimetry on those extravasations to test these globally accepted hypotheses.Results: A literature review found 58 peer-reviewed documents suggesting patient harm. Adverse event/vigilance report database reviews for extravasations were conducted and revealed 38 adverse events which listed diagnostic radiopharmaceutical extravasation as a factor, despite a regulatory exemption for required reporting. In our own case material, assessment of care was evaluated for five extravasated patients who underwent repeat imaging. Findings reflected results of literature review and included mis- or non-identification of lesions, underestimation of Standardized Uptake Values (SUVs) by 19–73%, classification of scans as non-diagnostic, and the need to repeat imaging with the associated additional radiation exposure, inconvenience, or delays in care. Dosimetry was performed for the same five cases of diagnostic radiopharmaceutical extravasation. Absorbed doses to 5 cm3 of tissue were between 1.1 and 8.7 Gy, and shallow dose equivalent for 10 cm2 of skin was as high as 4.2 Sv.Conclusions: Our findings suggest that significant extravasations can or have caused patient harm and can irradiate patients' tissue with doses that exceed medical event reporting limits and deterministic effect thresholds. Therefore, diagnostic radiopharmaceutical injections should be monitored, and dosimetry of extravasated tissue should be performed in certain cases where thresholds are thought to have been exceeded. Process improvement efforts should be implemented to reduce the frequency of extravasation in nuclear medicine.