Telehealth and Telemedicine: Regulatory and Medicolegal Landscape.

ABSTRACT: Telehealth and telemedicine experienced remarkable growth during and after the recent COVID-19 pandemic. Telehealth is generally defined as nonclinical services that employ telecommunication technology. Telemedicine refers more specifically to remote clinical services including diagnosis, monitoring, and treatment. Nuclear medicine is no exception in employing telemedicine increasingly in clinical practice for image interpretation and treatment consultation and care delivery supervision. There is no doubt that soon, the use of tele-nuclear medicine will increase, comparable to the employment of telecommunication in other fields of medicine. We review the medicolegal and regulatory aspects of the evolution in the clinical practice of medicine through telehealth and telemedicine.

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

Clinical Trials of Prostate-Specific Membrane Antigen Radiopharmaceutical Therapy.

Prostate-specific membrane antigen (PSMA) theranostics has been a momentous triumph for nuclear medicine. The recent approvals of PSMA-targeted imaging agents (68Ga-PSMA-11, 18F-DCFPyL) and radiopharmaceutical therapy (177Lu-PSMA-617) have paved the way for theranostics as a viable care strategy for men with metastatic castration-resistant prostate cancer. The imaging clinical trials OSPREY, CONDOR, and those conducted at the University of California (Los Angeles and San Francisco), as well as the randomized phase 3 therapy trial VISION, have been the fruitful beginnings for PSMA theranostics. There are currently several ongoing clinical trials to expand the reach of PSMA theranostics to the earlier phases of prostate cancer and to optimize its utility in combination therapeutic regimens. We provide a brief narrative review of the many PSMA-directed radiopharmaceutical therapy clinical trials with the ß-emitter 177Lu-PSMA-617 and the α-emitter 225Ac-PSMA-617 in prostate cancer.

Integrating Theranostics Into Patient Care Pathways: AJR Expert Panel Narrative Review.

Theranostics describes the coupling of a diagnostic biomarker and a therapeutic agent (i.e., a theranostic pair) that have a common target in tumor cells or their microenvironment. The term is increasingly associated with in vivo nuclear medicine oncologic applications that couple diagnostic imaging by means of gamma radiation with concomitant localized high-energy particulate radiation to a tissue expressing the common target. Several theranostic pairs have been translated into clinical practice in the United States and are poised to become a mainstay of cancer treatment. The purposes of this article are to review experience with theranostics for solid-organ malignancies and to address the practical integration into care pathways of ß-emitting therapies that include somatostatin analogue radioligands for neuroendocrine tumors, PSMA-directed therapy for prostate cancer, and 131I-MIBG therapy for tumors of neural crest origin. Toxicities related to theranostics administration and indications for cessation of therapy in patients who experience adverse events are also discussed. A multidisciplinary team-based approach for identifying patients most likely to respond to these agents, determining the optimal time for therapy delivery, and managing patient care throughout the therapeutic course is critical to the success of a radiotheranostic program.

Tracking Docetaxel-Induced Cellular Proliferation Changes in Prostate Tumor-Bearing Mice with 18F-FMAU PET.

OBJECTIVES: The aim of this exploratory preclinical study was to evaluate the efficacy of 18F-FMAU PET in quantitatively measuring cellular proliferation changes in response to a chemotherapeutic agent in experimental prostate cancer models. METHODS AND MATERIALS: Docetaxel (DTX) ‒ a standard therapy agent in castrate-resistant metastatic prostate cancer was used as the chemotherapy drug. Athymic male nu/nu mice were inoculated with PC-3 cells in the right flank. After the tumor diameter reached 5 mm, DTX (24 mg/kg) was injected intravenously twice a week, whereas the control group was intravenously administered with saline. The tumor size and body weight were monitored, and longitudinal PET scans were acquired with 18F-FMAU to evaluate tumor cellular proliferation. 18F-FMAU PET scans were performed at 2 hours post-injection of 18F-FMAU on days 0, 11, 18, and 22. Biodistribution studies were carried out after the PET scan on day 22. RESULTS: Consecutive administrations of DTX were effective in inhibiting PC-3 tumor growth compared to the control group. For PET imaging, PC-3 tumor uptake of 18F-FMAU in the DTX group was increased significantly from 3.09 ± 0.60 %ID/g (day 0) to 5.32 ± 0.37 %ID/g (day 22), whereas the 18F-FMAU tumor update in the control group remained relatively stable on day 0 (2.37 ± 0.51 %ID/g) vs. day 22 (1.83 ± 0.22 %ID/g). The tumor-to-muscle uptake ratio of 18F-FMAU was increased from 2.63 ± 0.20 (day 0) to 5.91 ± 1.1 (day 22) in the DTX group. On day 22, no statistical significance was observed in the tumor-to-muscle uptake ratio of 18F-FMAU in the DTX group vs. the control group. The tumor-to-liver uptake ratio of 18F-FMAU was also similar on day 22 in the DTX group (4.29 ± 0.09) vs. the control group (3.83 ± 0.59). CONCLUSION: 18F-FMAU uptake in implanted PC-3 tumors increases with DTX despite inhibiting tumor growth. Further investigation is needed to decipher the underlying biological mechanism of this apparent flare effect and its relation to the predictability of tumor response to DTX.

Oligometastatic Prostate Cancer: Current Status and Future Challenges.

In accordance with the spectrum theory of metastatic disease, an oligometastatic clinical state has been proposed as an intermediary step along the natural history of cancer with few (typically 1-3) metastatic lesions identifiable on imaging that may be amenable to metastasis-directed therapy. Effective therapy of oligometastatic disease is anticipated to impact cancer evolution by delaying progression and improving patient outcome at a minimal or acceptable cost of toxicity. There has been increasing recognition of oligometastatic disease in prostate cancer with the advent of new-generation imaging agents, most notably the recently approved PET radiotracers based on targeting prostate-specific membrane antigen. Early clinical trials with metastasis-directed therapy of oligometastases have provided evidence for delaying the employment of systematic therapy and improving outcome in selected patients. Despite these encouraging results, much needs to be investigated and learned about the underlying biology of the oligometastatic state along the evolutionary clinical course of prostate cancer, the identification of relevant imaging and nonimaging predictive and prognostic biomarkers, and the development of treatment strategies to optimize short-term and long-term patient outcome. We provide a review of the current status and the lingering challenges of this rapidly evolving clinical space in prostate cancer.

Molecular Imaging Assessment of Androgen Deprivation Therapy in Prostate Cancer.

Hormonal therapy has long been recognized as a mainstay treatment for prostate cancer. New generation imaging agents have provided unprecedented opportunities at all phases along the natural history of prostate cancer. We review the literature on the effect of androgens and androgen deprivation therapy on prostate tumor at its various biological phases using the new generation molecular imaging agents in conjunction with positron emission tomography.

Management Impact of Metachronous Oligometastatic Disease Identified on 18F-Fluciclovine (Axumin™) PET/CT in Biochemically Recurrent Prostate Cancer.

PURPOSE: We assessed the incidence rate and management impact of oligometastatic disease detected on 18F-fluciclovine (Axumin™) PET/CT in men with first biochemical recurrence (BCR) of prostate cancer (PCA) after definitive primary therapy. METHODS AND MATERIALS: We retrospectively reviewed our clinical database for men with PCA who underwent 18F-fluciclovine PET/CT for imaging evaluation of BCR with negative or equivocal findings on conventional imaging. We included patients with up to and including 5 metastases (oligometastases) regardless of imaging evidence for local recurrence in the treated prostate bed. We examined the association between mean serum prostate specific antigen (PSA) levels with the number of oligometastases (non-parametric ANOVA) and between patients with or without local recurrence (Student t-test). The management impact of oligometastatic disease was tabulated. RESULTS: We identified 21 patients with oligometastases upon first BCR (PSA 0.2-56.8 ng/mL) out of 89 eligible patients. There was a significant difference (p = 0.04) in the mean PSA levels between patients with local recurrence (n = 12) and those without local recurrence (n = 9). In the subgroup of analysis of patients without local recurrence, there was no significant association between mean PSA level and number of oligometastases (p = 0.83). Distribution of oligometastases included 66.7% isolated nodal disease and 33.3% bone only. Twelve (57.1%) patients had change in management to include change in ADT, salvage therapy, or both. Treatment change was initiated in 62.5%, 28.6%, 66.7%, 100%, and 100% of patients with 1, 2, 3, 4, and 5 oligometastatic lesions, respectively. CONCLUSION: The incidence rate of oligometastatic disease in men with first BCR of PCA undergoing 18F-fluciclovine PET/CT for imaging evaluation of BCR was 23.6% in our eligible patient population. There was no significant association between serum PSA level and the number of oligometastases. Treatment management was affected in 57.1% of patients with oligometastases.

Joint EANM, SNMMI, and IAEA Enabling Guide: How to Set up a Theranostics Center.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumor such as prostate cancer requires the expansion of existing and the establishment of new theranostics centers. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostic centers. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Joint EANM, SNMMI and IAEA enabling guide: how to set up a theranostics centre.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of existing and the establishment of new theranostics centres. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostics centres. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

The VISION Forward: Recognition and Implication of PSMA-/18F-FDG+ mCRPC.

Metastatic castration resistant prostate cancer (mCRPC) is incurable. The expression of the transmembrane protein prostate-specific membrane antigen (PSMA) is markedly increased in most mCRPC lesions. PSMA has been recognized as a viable biologic target for imaging and radionuclide therapy (theranostics) in mCRPC. The PET agents 68Ga-PSMA-11 and 18F-DCFPyL have recently been approved for imaging evaluation of patients with suspected metastasis who are candidates for initial definitive therapy and patients with suspected recurrence based on elevated serum prostate-specific antigen level. Radioligand therapy (RLT) with 177Lu-PSMA-617 (177Lu-vipivotide tetraxetan, Pluvicto, Novartis/AAA) was approved on March 23, 2022, based on the favorable results of the VISION trial. It has been recognized that PET imaging of PSMA expression and glucose metabolism (with 18F-FDG) provides a more comprehensive assessment of the tumor burden and heterogeneity. However, there are many unresolved issues that surround whether or not imaging with 18F-FDG PET is advantageous in the clinical setting of PSMA RLT in mCRPR.