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PET/CT is a commonly used modality in cancer imaging, as it can help in diagnosis, staging and assessment of treatment response in many cancer types. A better understanding of the tumor microenvironment and identification of multiple selective targets are promoting further investigation into different radiotracers for diagnosis and therapy. In the past few decades many radiopharmaceuticals have emerged for specific oncologic indications providing superior detection rate than some morphologic modalities. The purpose of this review is to provide an update on the most current radiopharmaceuticals used in cancer imaging including the mechanism of action, indications and pitfalls.

Background: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool., Patients and Methods: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11 C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) ( 18 F-FACBC), or Gallium-68-prostate-specific-membrane-antigen ( 68 Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809)., Results: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68 Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68 Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68 Ga-PSMA and 18 F-FACBC parameters and for major maximum standardized uptake value at the first 11 C-Choline PET scan., Conclusions: Our study highlighted that 11 C-Choline, 68 Ga-PSMA, and 18 F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68 Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA., Competing Interests: Disclosure FM has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD, and Pfizer outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Neuroendocrine neoplasms are rare and heterogenous group of tumors with varying degrees of clinical presentations and involvement of multiple organ systems in the body. In the modern clinical practice somatostatin receptor molecular imaging and targeted radioligand therapy plays a vital role in the diagnosis and management of the disease. Several new and promising radiotracers for NET imaging and theranostics, belonging to various groups and classes are being studied and investigated. This exponential growth of radiotracers poses concerns about the indication, clinical benefit, and safety profile of the agents. We discuss the basis behind these radiotracers clinical use, receptor targeting and intra and inter tumor heterogeneity. Furthermore, role of dual tracer imaging, combination therapy and potential applications of dosimetry in predicting treatment outcome and safety profile is reviewed. Individualized precision medicine with better tumor characterization, maximum therapeutic benefit and minimum toxicity is the way forward for future medicine., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest with the material presented in this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In cardiotoxicity, PET/MR affords an accurate evaluation of cardiovascular morphology, function, and also multi-parametric tissue characterization. A composite of several cardiac imaging parameters provided by the PET/MR scanner is likely to outperform a single parameter or imaging modality in the assessment and prediction of the severity and progression of cardiotoxicity but needing clinical investigations. Of particular interest, a heterogeneity map of single PET and CMR parameters could be perfectly correlated with the PET/MR scanner likely emerging as a promising marker of cardiotoxicity to monitor treatment response. While such functional and structural multiparametric imaging approach with cardiac PET/MR in the assessment and characterization of cardiotoxicity holds much promise, its validity and value in cancer patients treated with chemotherapy and/or radiation still needs to be assessed. The multi-parametric imaging approach with PET/MR, however, is likely to set new standards to develop predictive constellations of parameters for the severity and potential progression of cardiotoxicity that should afford timely and individualized treatment intervention to ascertain myocardial recovery and improved clinical outcome in these high-risk patients., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Advancements in brain imaging techniques have emerged as a significant tool in detecting Alzheimer's disease (AD) progression. The complicated cascade of AD progression can be detected using radio imaging, especially with Positron emission tomography (PET). The review focus on recently introduced investigational PET tracers targeting neurofibrillary tau aggregates found typically in AD. Herein, we also address the use of different PET tracers and the clinical implementation of established and newer generation tracers. This review also intends to discuss the importance of several PET radiotracers and challenges in PET imaging., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although it has been shown that trophic transfer of trace elements in oysters can be influenced by the diet, most of the studies investigating the ability of oysters to bioaccumulate trace elements from their diet are based on experiments using phytoplankton alone. Wild oysters feed also on large bacteria, ciliates or detritic organic matter. The present study aimed at examining the influence of food quality on the assimilation efficiency (AE) of trace elements in the Pacific cupped oyster Crassostrea gigas. Oysters were exposed via their food to the radiotracers of essential ( 57 Co, 54 Mn and 65 Zn) and non-essential ( 110m Ag, 241 Am and 109 Cd) trace elements under different diets (protozoan ciliates Uronema marinum and diatoms Thalassiosira pseudonana). Significant differences were found only for Ag and 241 Am, with lower AEs measured in oysters fed with ciliates than in individuals fed with diatoms (Ag: 54 ± 3% vs. 67 ± 4% and 241 Am: 62 ± 4% vs. 76 ± 4%). Interestingly, no significant difference was found among estimated depuration rates (k el ) for all trace elements ingested with the two diets tested. These findings indicate that the differences observed are driven by the digestion process, presumably due to difference of bioavailability of trace elements dependent on the quality of the food ingested., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) with different radiotracers enable regional evaluation of blood flow and glucose metabolism, of receptors and transporters of several molecules, and of abnormal deposition of peptides and proteins in the brain. The cerebellum has been used as a reference region for different radiotracers in several disease conditions. Whole-brain voxel-wise analysis is not affected by a priori knowledge bias and should be preferred. SPECT and PET have contributed to establishing the cerebellum role in motion, cognition, and emotion control in physiologic and pathophysiologic conditions. The basic abnormal imaging findings include decreased or increased uptake of flow or metabolism tracers in the cerebellum alone or as part of a network. Decreased uptake is generally observed in primary structural damage of the cerebellum, but can also represent a distant effect of cerebral damage (crossed diaschisis). Increased uptake can be observed in Freidreich ataxia, inflammatory or immune-mediated diseases of the cerebellum, and in status epilepticus. The possibility is also recognized that primary structural damage of the cerebellum might determine distance effects on other brain structures (reversed diaschisis). So far, SPECT and PET have been predominantly used in clinical studies to investigate cerebellar changes in neurologic and psychiatric diseases and in connection with pharmacologic, transcranial magnetic stimulation, deep-brain stimulation, or surgical treatments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The production of 18 F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse 18 F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [ 18 F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield., Methods: [ 18 F]MEL050, [ 18 F]Fallypride and [ 18 F]PBR111 were radiolabeled with [ 18 F]fluoride using the Advion NanoTek Microfluidic Synthesis System. The outlet of the microreactor was connected to an automated HPLC injector and following the collection of the product, SPE reformulation produced the 18 F-radiotracer in <10% ethanolic saline. A thorough automated cleaning procedure was implemented to ensure no cross-contamination between radiotracer synthesis., Results: The complete productions for [ 18 F]MEL050 and [ 18 F]Fallypride were performed at total flow rates of 20μL/min, resulting in 40±13% and 25±13% RCY respectively. [ 18 F]PBR111 was performed at 200μL/min to obtain 27±8% RCY. Molar activities for each 18 F-radiotracer were >100GBq/μmol and radiochemical purities were >97%, implying that the cleaning procedure was effective., Conclusions: Using the same initial solution of [ 18 F]fluoride, microreactor, HPLC column and SPE cartridge, three diverse 18 F-radiotracers could be produced in yields sufficient for preclinical studies in a back-to-back fashion using a microfluidic system with no detectable cross-contamination., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

The periphyton associated with freshwater macrophyte roots is the main site of Hg methylation in different wetland environments in the world. The aim of this study was to test the use of connectivity metrics of water bodies, in the context of patches, in a tropical waterscape wetland (Guapore River, Amazonia, Brazil) as a predictor of potential net methylmercury (MeHg) production by periphyton communities. We sampled 15 lakes with different patterns of lateral connectivity with the main river channel, performing net mercury methylation potential tests in incubations with local water and Eichhornia crassipes root-periphyton samples, using (203)HgCl2 as a tracer. Physico-chemical variables, landscape data (morphological characteristics, land use, and lateral connection type of water bodies) using GIS resources and field data were analyzed with Generalized Additive Models (GAM). The net Me(203)Hg production (as % of total added (203)Hg) was expressive (6.2-25.6%) showing that periphyton is an important matrix in MeHg production. The model that best explained the variation in the net Me(203)Hg production (76%) was built by the variables: connection type, total phosphorus and dissolved organic carbon (DOC) in water (AICc=48.324, p=0.001). Connection type factor was the best factor to model fit (r(2)=0.32; p=0.008) and temporarily connected lakes had higher rates of net mercury methylation. Both DOC and total phosphorus showed positive significant covariation with the net methylation rates (r(2)=0.26; p=0.008 and r(2)=0.21; p=0.012 respectively). Our study suggests a strong relationship between rates of net MeHg production in this tropical area and the type of water body and its hydrological connectivity within the waterscape., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: In this study two (111)In-labeled dimeric cyclic RGD peptides, (111)In(DOTA-Galacto-RGD2) and (111)In(DOTA-3P-RGD2), were evaluated as radiotracers for breast tumor imaging. The objective was to evaluate the impact of SAA, PEG2 and 1,2,3-triazole linkers as compare to PEG4 on the tumor uptake and excretion kinetics of (111)In radiotracers., Methods: DOTA-Galacto-RGD2 was prepared by conjugation of Galacto-RGD2 with DOTA-OSu in the presence of diisopropylethylamine. Its integrin αvβ3 binding affinity was determined using a whole-cell displacement assay against (125)I-echistatin bound to U87MG glioma cells, and was compared with those of c(RGDfK), DOTA-3P-RGD2 and DOTA-3P-RGK2 (a nonsense peptide conjugate with "scrambled" RGK sequences). (111)In(DOTA-Galacto-RGD2) and (111)In(DOTA-3P-RGD2) were prepared and evaluated for their tumor-targeting capability and biodistribution properties in athymic nude mice bearing MDA-MB-435 breast tumor xenografts. Planar imaging studies were performed to demonstrate the utility of (111)In(DOTA-Galacto-RGD2) and (111)In(DOTA-3P-RGD2) for breast tumor imaging., Results: IC50 values of DOTA-Galacto-RGD2, DOTA-3P-RGD2, and DOTA-3P-RGK2 were calculated to be 27±2, 29±4, 596±48nM, respectively. The tumor uptake values of (111)In(DOTA-Galacto-RGD2) (6.79±0.98, 6.56±0.56, 4.17±0.61 and 1.09±0.13 %ID/g at 1, 4, 24 and 72hours p.i., respectively) were almost identical to those of (111)In(DOTA-3P-RGD2) (6.17±1.65, 5.94±0.84, 3.40±0.50 and 0.99±0.20 %ID/g, respectively). (111)In(DOTA-Galacto-RGD2) had a faster clearance from blood and muscle than (111)In(DOTA-3P-RGD2), leading to higher tumor/blood and tumor/muscle ratios. (111)In(DOTA-3P-RGD2) had lower liver uptake and better tumor/liver ratios than (111)In(DOTA-Galacto-RGD2). The tumor uptake of (111)In(DOTA-Galacto-RGD2) and (111)In(DOTA-3P-RGD2) was both integrin αvβ3 and RGD-specific. Imaging data suggest that (111)In(DOTA-Galacto-RGD2) and (111)In(DOTA-3P-RGD2) are useful as radiotracers for imaging integrin αvβ3-positive breast tumors., Conclusion: The results from this study suggest that replacing PEG4 linkers between two RGD moieties with a pair of SAA, PEG2 and 1,2,3-triazole groups has little impact on integrin αvβ3 binding affinity and tumor uptake of (111)In-labeled dimeric cyclic RGD peptides. Despite the subtle differences in their excretion kinetics from noncancerous tissues, (111)In(DOTA-Galacto-RGD2) and (111)In(DOTA-3P-RGD2) are useful radiotracers for imaging integrin αvβ3-positive breast tumors., (Copyright © 2014 Elsevier Inc. All rights reserved.)