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Synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are characterized by the aggregation of α-synuclein. Variations in brain distribution allow for differentiation among these diseases and facilitate precise clinical diagnosis. However, distinguishing between synucleinopathies and Parkinsonism with tauopathies poses a challenge, significantly impacting clinical drug development. Therefore, molecular imaging is crucial for synucleinopathies, particularly for clinical diagnosis, assessment of drug efficacy, and disease surveillance. In recent years, advances in molecular imaging have led to rapid development of α-synuclein-specific tracers for positron emission tomography (PET), most of which are still in pre-clinical stages. Interestingly, some of these tracers share similar compound skeletal structures and are currently undergoing optimization for clinical application. Despite this progress, there remain challenges in developing α-synuclein tracers. This review summarizes recent findings on promising PET tracers and discusses representative compounds' characteristics while offering suggestions for further research orientation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Vicarious excretion of tracer and contrast media is a known phenomenon and is not fully understood [1,2]. We report a case of unexpected vicarious excretion of 99m Tc-pyrophosphate in the gallbladder seen on a scan performed to evaluate suspected cardiac amyloidosis, which is the first report of this phenomenon to the best of our knowledge., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

The cannabinoid type 2 receptor (CB2) has been implicated in a variety of central and peripheral inflammatory diseases, prompting significant interest in the development of CB2-targeted diagnostic and therapeutic agents. A validated positron emission tomography (PET) radioligand for imaging CB2 in the living human brain as well as in peripheral tissues is currently lacking. As part of our research program, we have recently identified the trisubstituted pyridine, [ 18 F]RoSMA-18-d 6 , which proved to be highly suitable for in vitro and in vivo mapping of CB2 in rodents. The aim of this study was to assess the performance characteristics of [ 18 F]RoSMA-18-d 6 in nonhuman primates (NHPs) to pave the way for clinical translation. [ 18 F]RoSMA-18-d 6 was synthesized from the respective tosylate precursor according to previously reported procedures. In vitro autoradiograms with NHP spleen tissue sections revealed a high binding of [ 18 F]RoSMA-18-d 6 to the CB2-rich NHP spleen, which was significantly blocked by coincubation with the commercially available CB2 ligand, GW405833 (10 μM). In contrast, no specific binding was observed by in vitro autoradiography with NHP brain sections, which was in agreement with the notion of a CB2-deficient healthy mammalian brain. In vitro findings were corroborated by PET imaging experiments in NHPs, where [ 18 F]RoSMA-18-d 6 uptake in the spleen was dose-dependently attenuated with 1 and 5 mg/kg GW405833, while no specific brain signal was observed. Remarkably, we observed tracer uptake and retention in the NHP spinal cord, which was reduced by GW405833 blockade, pointing toward a potential utility of [ 18 F]RoSMA-18-d 6 in probing CB2-expressing cells in the bone marrow. If these observations are substantiated in NHP models of enhanced leukocyte proliferation in the bone marrow, [ 18 F]RoSMA-18-d 6 may serve as a valuable marker for hematopoietic activity in various pathologies. In conclusion, [ 18 F]RoSMA-18-d 6 proved to be a suitable PET radioligand for imaging CB2 in NHPs, supporting its translation to humans.

Objectives: To enable non-invasive real-time quantification of vasopressin 1A (V1A) receptors in peripheral organs, we sought to develop a suitable PET probe that would allow specific and selective V1A receptor imaging in vitro and in vivo., Methods: We synthesized a high-affinity and -selectivity ligand, designated compound 17. The target structure was labeled with carbon-11 and tested for its utility as a V1A-targeted PET tracer by cell uptake studies, autoradiography, in vivo PET imaging and ex vivo biodistribution experiments., Results: Compound 17 (PF-184563) and the respective precursor for radiolabeling were synthesized in an overall yield of 49% (over 7 steps) and 40% (over 8 steps), respectively. An inhibitory constant of 0.9 nM towards the V1A receptors was measured, while excellent selectivity over the related V1B, V2 and OT receptor (IC 50 >10,000 nM) were obtained. Cell uptake studies revealed considerable V1A binding, which was significantly reduced in the presence of V1A antagonists. Conversely, there was no significant blockade in the presence of V1B and V2 antagonists. In vitro autoradiography and PET imaging studies in rodents indicated specific tracer binding mainly in the liver. Further, the pancreas, spleen and the heart exhibited specific binding of [ 11 C]17 ([ 11 C]PF-184563) by ex vivo biodistribution experiments., Conclusion: We have developed the first V1A-targeted PET ligand that is suitable for subtype-selective receptor imaging in peripheral organs including the liver, heart, pancreas and spleen. Our findings suggest that [ 11 C]PF-184563 can be a valuable tool to study the role of V1A receptors in liver diseases, as well as in cardiovascular pathologies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cancer-associated fibroblasts constitute a vital subpopulation of the tumor stroma and are present in more than 90% of epithelial carcinomas. The overexpression of the serine protease fibroblast activation protein (FAP) allows a selective targeting of a variety of tumors by inhibitor-based radiopharmaceuticals (FAPIs). Of these compounds, FAPI-04 has been recently introduced as a theranostic radiotracer and demonstrated high uptake into different FAP-positive tumors in cancer patients. To enable the delivery of higher doses, thereby improving the outcome of a therapeutic application, several FAPI variants were designed to further increase tumor uptake and retention of these tracers. Methods: Novel quinoline-based radiotracers were synthesized by organic chemistry and evaluated in radioligand binding assays using FAP-expressing HT-1080 cells. Depending on their in vitro performance, small-animal PET imaging and biodistribution studies were performed on HT-1080-FAP tumor-bearing mice. The most promising compounds were used for clinical PET imaging in 8 cancer patients. Results: Compared with FAPI-04, 11 of 15 FAPI derivatives showed improved FAP binding in vitro. Of these, 7 compounds demonstrated increased tumor uptake in tumor-bearing mice. Moreover, tumor-to-normal-organ ratios were improved for most of the compounds, resulting in images with higher contrast. Notably two of the radiotracers, FAPI-21 and -46, displayed substantially improved ratios of tumor to blood, liver, muscle, and intestinal uptake. A first diagnostic application in cancer patients revealed high intratumoral uptake of both radiotracers already 10 min after administration but a higher uptake in oral mucosa, salivary glands, and thyroid for FAPI-21. Conclusion: Chemical modification of the FAPI framework enabled enhanced FAP binding and improved pharmacokinetics in most of the derivatives, resulting in high-contrast images. Moreover, higher doses of radioactivity can be delivered while minimizing damage to healthy tissue, which may improve therapeutic outcome., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been made to develop a suitable 5-HT2A R positron emission tomography-tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5-HT2A R radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning outcomes that can be made from these tracer development processes., (Copyright © 2015 John Wiley & Sons, Ltd.)

Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been made to develop a suitable 5-HT2AR positron emission tomography-tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5-HT2AR radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning outcomes that can be made from these tracer development processes. [ABSTRACT FROM AUTHOR]

Purpose: Peptides with restricted conformation provide increased affinity and stability against degradation as compared to linear peptides. This study investigates the characteristics of derivatives of the sunflower trypsin inhibitor 1 (SFTI-1), a 14 amino acid peptide with high intrinsic stability.Methods: Three SFTI-1 derivatives (cyclic cSFTI, acyclic oSFTI, and DOTA-SFTI) were generated by Fmoc-based automated synthesis. Thereafter, the inhibitory activity for trypsin was determined. After radiolabeling, kinetic and competition studies were done in a variety of tumor cell lines including prostate carcinoma, colon carcinoma, mammary carcinoma, and hepatoma to characterize the binding affinity of the peptides. The stability was determined by incubating the molecules in human serum for increasing time periods. Furthermore, the biodistribution was measured in nude mice bearing human prostate carcinomas.Results: The inhibitory constants for trypsin inhibition were 0.08 nM (cSFTI), 0.15 nM (oSFTI), and 0.3 nM (DOTA-SFTI). Among the different tumor cell lines evaluated, the prostate cancer cell lines PC-3 and DU-145 showed the highest accumulation of the radiolabeled peptides. The open-chain derivatives generally bound better than the cyclic one. Binding was constant during 4 h and could be competed by addition of the cold peptide up to 75%. The stability in serum revealed half-lives of 75.8 h for cSFTI, 34.5 h for oSFTI, and 41.7 h for DOTA-SFTI. The biodistribution showed a rapid renal clearance for all three compounds and tumor uptake values up to 3%ID/g.Conclusions: SFTI derivatives are small stable molecules readily accessible by solid-phase synthesis. The trypsin inhibition was not influenced by the cyclization, and addition of a chelator had no significant influence. The exceptional rigidity and stability allow the use of SFTI derivatives as scaffolds for the introduction of tumor-specific peptide motifs which could be used to increase cell-binding affinities and thus their use as diagnostic and/or therapeutic tools. [ABSTRACT FROM AUTHOR]