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Introduction: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging., Evidence Acquisition: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations., Evidence Synthesis: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident., Conclusions: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

Immune checkpoint inhibitors (ICI) represent a cornerstone in cancer treatment. However, the peculiarity of immune response, determining distinctive response patterns and toxicity events, challenges the conventional response criteria. Therefore, the effective tumor response and the real clinical benefit cannot be demonstrated adequately. In this context, recent studies using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]) positron emission tomography/computed tomography (PET/CT) have shown promising results for therapeutic monitoring during ICI, although further research is needed to confirm its potentials. In this review, we focus on the latest evidences and challenges regarding the assessment of morphological and metabolic parameters in the evaluation of ICI therapy. We will also discuss a wide range of emerging imaging-based biomarkers for anti-checkpoint therapy as well as their challenges in the clinical practice.

Tumor response is often used as a surrogate marker for survival practically in all clinical trials. Therefore, robust and valid response criteria during the course of trials are fundamental for the assessment of response to therapy. This aspect, however, becomes particularly challenging when it comes to bone metastases. In the era of targeted therapies and immune-checkpoint inhibitors (ICI), response assessment by morphologic-based criteria cannot detect the real tumor response and, consequently, fail to demonstrate the actual clinical benefit. This review will focus on some of the most common morphologic and metabolic response criteria and their application for bone lesions, highlighting relative strengths and weaknesses as well as potential future methods in the era of target therapies and immunotherapy with ICI.

The use of radiopharmaceuticals is the distinguishing characteristics of nuclear medicine. Among the panel of available radiopharmaceuticals in many PET centers around the world, choline is well represented, being widely used to image prostate cancer. Carbon-11 labelled choline can only be produced in centres with a cyclotron available, but the 18F-labelled radiopharmaceutical is distributed and licensed in several countries in Europe. Besides prostate cancer, other possible uses of choline are related to its ability to indirectly evaluate the cell proliferation as a measure of the synthesis of lipids required for cell membrane. In particular, the radiopharmaceutical can be successfully used in those districts where 18F-FDG has a high uptake, like the brain. Moreover, slow growing tumors, not always taking up 18F-FDG, like hepatocellular carcinoma, can also be imaged. We will evaluate possibly uses of this molecule in patients affected by prostate cancer, brain tumors and hepatocellular carcinoma.

Gallium-68 DOTANOC is a high affinity somatostatin receptor ligand, first introduced in 2005 for imaging neuroendocrine tumors. Due to its technically simple production, broad availability, favourable biodistribution and advantageous dosimetry, although not approved yet in all European countries, gallium-68 DOTANOC has rapidly gained acceptance in the diagnostic and therapeutic work-flow of different types of neuroendocrine tumors. Principal indications in clinical practice in countries where it is officially approved include diagnosis and staging, restaging after treatment, identification of sites of unknown primary and selection of patients with neuroendocrine tumors eligible for therapy with somatostatin analogues.

123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.

Aim: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration., Methods: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR)., Results: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT., Conclusion: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

Aim: Despite its established utility in non-Hodgkin's lymphoma, not much is reported on FDG positron emission tomography (PET) with respect to radioimmunotherapy (RIT). In this paper we investigate its value in patients affected by follicular lymphoma (FL) before and after treatment with [90Y]Ibritumomab Tiuxetan (Zevalin(R))., Methods: We evaluated 38 relapsed or refractory FL patients. All had a PET scan performed before and 3 months after radioimmunotherapy. Final assessment was done 9 months post-RIT, including clinical evaluation, other imaging techniques and/or biopsy, when necessary., Results: At the first PET scan 20 patients out of 38 had a limited disease (nodal involvement on one side of the diaphragm: 7 above and 13 below), 11 patients had nodal findings on both sides of the diaphragm and the remaining 7 patients had both nodal and extra-nodal findings. At three months post-RIT, 21 patients (55%) were in complete remission, 13 patients (34%) had a partial response (PR) and four patients (11%) had a progression disease (PD). The corresponding rates at final assessment were all consistent with the 3-month evaluation: 55% CR, 13% PR and 32% PD. FDG PET scan revealed maximal predictive values. When comparing the disease extent at relapse and the response to treatment, we could testify a higher rate of CR (75%) in patients with limited disease, while in patients with diffused nodal and/or extra-nodal findings, it was more frequent a PR or PD (66%)., Conclusion: Our data are concordant with the expected results on RIT, and FDG PET is confirmed to be useful in assessing treatment response. Potential correlation can also be picked out between the disease extent at relapse and the CR rate, with reasonable PET predictivity for the final outcome.