Molecular Imaging of Vulnerable Coronary Plaque with Radiolabeled Somatostatin Receptors (SSTR)

Atherosclerosis is responsible for the majority of heart attacks and is characterized by several modifications of the arterial wall including an inflammatory reaction. The silent course of atherosclerosis has made it necessary to develop predictors of disease complications before symptomatic lesions occur. Vulnerable to rupture atherosclerotic plaques are the target for molecular imaging. To this aim, different radiopharmaceuticals for PET/CT have emerged for the identification of high-risk plaques, with high specificity for the identification of the cellular components and pathophysiological status of plaques. By targeting specific receptors on activated macrophages in high-risk plaques, radiolabelled somatostatin analogues such as 68Ga-DOTA-TOC, TATE,0 or NOC have shown high relevance to detect vulnerable, atherosclerotic plaques. This PET radiopharmaceutical has been tested in several pre-clinical and clinical studies, as reviewed here, showing an important correlation with other risk factors.

Analytical procedure for quality control of 18F-Choline radiopharmaceutical

18Fluoromethylcholine (18F-Choline, 18F-FCH) has been produced using a home-made automatic synthesiser at 30 MeV Cyclotron Centre, 108 Military Central Hospital. In order to be licensed using for patients, the 18F-FCH radiopharmaceutical needs to meet the required quality specifications listed in the pharmacopeia. The objective of this study was to build up the analytical procedure and to perform for the 18F-FCH quality control followed the EuPh2017 pharmacopeia for the PET radiopharmaceutical. The result obtained confirmed that the total time to complete the test of one sample of the 18F-FCH was less than 35 min. Identifications of 18F-FCH, radiochemical purity, and 18F content were determined with accuracy >96% by High-performance liquid chromatography (HPLC) method and content of residual solvents consists of Ethanol, Acetonitrile, Dibromomethane, Dimethylethanolamine were determined with the accuracy >97% by Gas chromatography (GC) method.

Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer

Purpose This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. Methods Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35–45, 60–88 and 90–118 min. Net influx rates (Ki) were calculated using Patlak plots. Results Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. Conclusion 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. Trial Registration NCT03995888 (24 June 2019).

[18F]F13640, a 5-HT1A Receptor Radiopharmaceutical Sensitive to Brain Serotonin Fluctuations

IntroductionSerotonin is involved in a variety of physiological functions and brain disorders. In this context, efforts have been made to investigate the in vivo fluctuations of this neurotransmitter using positron emission tomography (PET) imaging paradigms. Since serotonin is a full agonist, it binds preferentially to G-protein coupled receptors. In contrast, antagonist PET ligands additionally interact with uncoupled receptors. This could explain the lack of sensitivity to serotonin fluctuations of current 5-HT1A radiopharmaceuticals which are mainly antagonists and suggests that agonist radiotracers would be more appropriate to measure changes in neurotransmitter release. The present study evaluated the sensitivity to endogenous serotonin release of a recently developed, selective 5-HT1A receptor PET radiopharmaceutical, the agonist [18F]F13640 (a.k.a. befiradol or NLX-112).Materials and MethodsFour cats each underwent three PET scans with [18F]F13640, i.e., a control PET scan of 90 min, a PET scan preceded 30 min before by an intravenous injection 1 mg/kg of d-fenfluramine, a serotonin releaser (blocking challenge), and a PET scan comprising the intravenous injection of 1 mg/kg of d-fenfluramine 30 min after the radiotracer injection (displacement challenge). Data were analyzed with regions of interest and voxel-based approaches. A lp-ntPET model approach was implemented to determine the dynamic of serotonin release during the challenge study.ResultsD-fenfluramine pretreatment elicited a massive inhibition of [18F]F13640 labeling in regions known to express 5-HT1A receptors, e.g., raphe nuclei, hippocampus, thalamus, anterior cingulate cortex, caudate putamen, occipital, frontal and parietal cortices, and gray matter of cerebellum. Administration of d-fenfluramine during PET acquisition indicates changes in occupancy from 10% (thalamus) to 31% (gray matter of cerebellum) even though the dissociation rate of [18F]F13640 over the 90 min acquisition time was modest. The lp-ntPET simulation succeeded in differentiating the control and challenge conditions.ConclusionThe present findings demonstrate that labeling of 5-HT1A receptors with [18F]F13640 is sensitive to serotonin concentration fluctuations in vivo. Although the data underline the need to perform longer PET scan to ensure accurate measure of displacement, they support clinical development of [18F]F13640 as a tool to explore experimental paradigms involving physiological or pathological (neurological or neuropsychiatric pathologies) fluctuations of extracellular serotonin.

Pictorial essay: incidental findings on 18F-Fluciclovine PET/CT scan

Introduction Fluorine-18 (18F) Fluciclovine (anti-1-amino-3-18F-fluorocyclobutane- 1-carboxylic acid [FACBC]) is a synthetic amino acid labeled with 18F, currently used as PET radiopharmaceutical to investigating prostate cancer, namely in the recurrent setting. Fluciclovine is transported to cell membranes by amino acid transporters, such as LAT1 and ASCT2. The upregulation of LAT-1 and ASCT2 activities is typical of prostate cancer but is also present in other pathological conditions such as non-prostatic neoplasms (e.g., lung cancer) and in benign inflammatory process (e.g., benign prostatic hyperplasia, chronic prostatitis, high-grade prostatic hyperplasia intraepithelial). Methods In this short essay we present a retrospective FACBC PET/CT analysis consisting of a selection of the five most relevant cases of patients referred in our centre to FACBC PET/CT for prostate cancer, with concomitant FACBC uptake in sites atyipical for prostate cancer. Results These five selected cases demonstrate FACBC uptake at the level of the pancreatic head, adrenal incidentalomas, pulmonary nodules, mediastinal lymph nodes and neoformative tissue of the rectal wall. Discussion Clinical cases selected in this pictorial essay have demonstrated that Fluciclovine is not an exclusive and specific radiotracer for prostate cancer and, therefore, can induce misdiagnosis. In fact, incidental benign and malignant uptake might occur and should be further evaluated with clinical correlation or other imaging.

Fully Automated Radiosynthesis of [18f]lbt999on Tracerlab Fxfn and Allinonemodules, A Pet Radiopharmaceutical for Imaging the Dopamine Transporter in Human Brain

Background:Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3b-p-tolyl-8-aza-bicyclo[3.2.1]octane-2b-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for in vivoneuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 has been produced on a TRACERlabFXFN for the Phase I study but forPhase III and a potent industrial production transfer, production has been also implemented on AllinOne (AIO)system requiring single use cassette. Both productions methods are reported herein. Results:Automation of [18F]LBT999radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n=16), with a radiochemical purity higher than 99 %and a molar activity of 158GBq/µmol at the end of synthesis. The transfer on the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n=5), with a radiochemical purity better than 98% and a molar activity in average higher to 154 GBq/µmol at the end of synthesis. Quality controls of both methods met the specification for clinical application.Conclusion:Both modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time.The developments made on AIO as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements make this approach as the best for a potent industrial production of the [18F]LBT999 and a future wider use.