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Fibroblast activation protein (FAP) is a type-II membrane bound glycoprotein specifically expressed by activated fibroblasts almost exclusively in pathological conditions including arthritis, fibrosis and cancer. FAP is overexpressed in cancer-associated fibroblasts (CAFs) located in tumor stroma, and is known to be involved in a variety of tumor-promoting activities such as angiogenesis, proliferation, resistance to chemotherapy, extracellular matrix remodeling and immunosuppression. In most cancer types, higher FAP expression is associated with worse clinical outcomes, leading to the hypothesis that FAP activity is involved in cancer development, cancer cell migration, and cancer spread. Recently, various high selectivity FAP inhibitors (FAPIs) have been developed and subsequently used for positron emission tomography (PET) imaging of different pathologies. Considering the paucity of widely available and especially mainstream reliable radioligands in brain cancer PET imaging, and the poor survival rates of patients with certain types of brain cancer such as glioblastoma, FAPI-PET represents a major development in enabling the detection of small primary or metastatic lesions in the brain due to its biological characteristics and low background accumulation. In this work, we aim to summarize the potential avenues for use of FAPI-PET, from the basic biological processes to oncologic imaging and with a main focus on brain imaging., Competing Interests: JD is an employee of Siemens Medical Solutions who did not financially sponsor this work. The author(s) OB declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The remaining 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., (© 2023 Djekidel, Alsadi, Abi Akl, Bouhali and O' Doherty.)

68 Ga-DOTATATE PET/CT is widely used for the evaluation of neuroendocrine tumors. Some reports exist on its use in the management of neuroblastoma. Building on the prior reports as well as our previous experience in using this technique for initial staging, we propose to describe its practical benefits in restaging and response to therapy. We describe different aspects including supply logistics, preparation, spatial resolution, and other practical applications. Methods: We reviewed the medical records for 8 patients who were evaluated with 68 Ga-DOTATATE PET/CT at our institution over 2 y. A note was made of the patient and disease characteristics and the indication for PET imaging, and the results were retrospectively analyzed for feasibility, logistics, radiation exposure, and utility in answering the clinical question. Results: Eight children (5 girls and 3 boys; age range, 4-60 mo; median age, 30 mo) diagnosed with neuroblastoma were imaged with 68 Ga-DOTATATE PET/CT and 5 with 123 I-metaiodobenzylguanidine ( 123 I-MIBG) SPECT/CT over 2 y. Three 68 Ga-DOTATATE PET scans were done for staging, 10 for response evaluation, and 2 for restaging. 68 Ga-DOTATATE PET accurately identified neuroblastoma lesions suspected or seen on anatomic imaging. It has been shown to be more specific and more sensitive than 123 I-MIBG and at times also MRI. It had better spatial and contrast resolution than 123 I-MIBG. 68 Ga-DOTATATE PET was better than 123 I-MIBG SPECT/CT, CT, and MRI in the detection of early progression and viable tumor delineation for response assessment, as well as in target volume definition for external-beam radiotherapy and proton-beam radiotherapy. 68 Ga-DOTATATE PET was also better at assessing bony and bone marrow disease changes with time. Conclusion: 68 Ga-DOTATATE PET/CT offers added value and a superior edge to other imaging modalities in restaging and response assessment in neuroblastoma patients. Further multicenter evaluations in larger cohorts are needed., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Prostate specific membrane antigen (PSMA) ligand labeled with Lutetium-177 (177Lu) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). Several prospective and retrospective studies as well as clinical trials are completed or underway. This has ultimately led to the approval of this therapy by the US Food and Drug Administration (FDA) on March 23 2022. Our work aims to present a mini-review of the most recent research performed and the potential future directions of 177Lu-PSMA-radioligand therapy (RLT) for mCRPC patients., Main Body: For patients with mCRPCwho have met the eligibility criteria for 177Lu-PSMA RLT, numerous studies and trials are either ongoing or have been completed. The studies included in this review have reported overall biochemical response, defined as a prostate-specific antigen (PSA) decline of at least 50%, in at least 44% of patients with mCRPC. The median ranges of overall survival (OS) and radiographic progression-free survival (rPFS) were reported within 10.7-56 and 3.6-16 months, respectively. With data from several retrospective and prospective studies published, the safety of 177Lu-PSMA RLT in mCRPC has been confirmed and demonstrated by its low toxicity profile. Various studies have published pharmacokinetic/pharmacodynamic models to better understand the absorption, distribution, metabolism, and excretion of the RLT in this patient population. Findings have been published for 177Lu-PSMA RLT alone and in combination with other agents. We summarize their findings in our review., Conclusions: The efficacy of 177Lu-PSMA RLT for patients with mCRPC has been proven thus far with promising results: PSA response, OS and rPFS when used alone or in combination with other treatment options, relative to the standard treatment options alone. The low toxicity profile noted also proves the safety of 177Lu-PSMA RLT in these patients., (© The Author(s) 2022. Published by Oxford University Press.)

Although MRI is the workhorse of brain tumor initial evaluation and follow-up, there is a growing amount of data recommending the incorporation of amino-acid PET imaging at different stages of the management of these patients. Recent nuclear medicine and neuro-oncology clinical practice recommendations support the use of amino-acid imaging in brain tumor imaging. Considering 18 F-DOPA is FDA approved for the evaluation of parkinsonian syndromes, it could be used clinically for other valuable clinical indications such as brain tumor evaluations. This value seems to be well established in adults and has growing evidence for its use in pediatrics as well. We offer to present four pediatric brain tumor cases imaged with 18 F-DOPA and review the literature., (Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)