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The aim of this work is to compare [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 PET/CT as imaging agents in patients with prostate cancer (PCa). Comparisons were made by evaluating times and costs of the radiolabeling process, imaging features including pharmacokinetics, and impact on patient management. The analysis of advantages and drawbacks of both radioligands might help to make a better choice based on firm data. For [68Ga]Ga-PSMA-11, the radiochemical yield (RCY) using a low starting activity (L, average activity of 596.55 ± 37.97 MBq) was of 80.98 ± 0.05%, while using a high one (H, average activity of 1436.27 ± 68.68 MBq), the RCY was 71.48 ± 0.04%. Thus, increased starting activities of [68Ga]-chloride negatively influenced the RCY. A similar scenario occurred for [18F]PSMA-1007. The rate of detection of PCa lesions by Positron Emission Tomography/Computed Tomography (PET/CT) was similar for both radioligands, while their distribution in normal organs significantly differed. Furthermore, similar patterns of biodistribution were found among [18F]PSMA-1007, [68Ga]Ga-PSMA-11, and [177Lu]Lu-PSMA-617, the most used agent for RLT. Moreover, the analysis of economical aspects for each single batch of production corrected for the number of allowed PET/CT examinations suggested major advantages of [18F]PSMA-1007 compared with [68Ga]Ga-PSMA-11. Data from this study should support the proper choice in the selection of the PSMA PET radioligand to use on the basis of the cases to study.

BackgroundRecently it has been identified a short peptide that showed allosteric antagonism against C–C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-d-amino acid peptidic CCR2 inhibitor called extracellular loop 1 inverso (ECL1i), d(LGTFLKC) has been identified and labeled to obtain a new probe for positron emission tomography in pulmonary fibrosis, heart injury, abdominal aortic aneurysm inflammation, atherosclerosis, head and neck cancer. Our goal was to develop, optimize and validate an automated synthesis method for [68Ga]68Ga-DOTA-ECL1i to make it available for a broader community. The synthesis of [68Ga]68Ga-DOTA-ECL1i was done using the Scintomics GRP® module with the already estabilished synthesis template for [68Ga]68Ga-DOTATOC/[68Ga]68Ga-PSMA. The radiopharmaceutical production was optimized scaling down the amount of DOTA-ECL1i (from 50 to 10 μg), evaluating synthesis efficiency and relevant quality control parameters in accordance with the European Pharmacopeia.ResultsBest results were yielded with 20 μg DOTA-ECL1i and then the process validation was carried out by producing three different batches on three different days obtaining an optimal radiochemical yield (66.69%) as well as radiochemical purity (100%) and molar activity (45.41 GBq/µmol).Conclusions[68Ga]68Ga-DOTA-ECL1i was successfully synthesized and it is, thus, available for multi-dose application in clinical settings.

Glomerular filtration rates for individual kidneys can be measured semi-quantitatively by a gamma camera using [99mTc]Tc-DTPA, with limited diagnostic accuracy. A more precise measurement can be performed on a PET/CT scanner using the radiotracer [68Ga]Ga-EDTA, which has been validated in animal studies. The purpose of this study was to develop an easy kit-based synthesis of [68Ga]Ga-EDTA that is compliant with good manufacturing practice (GMP) and applicable for human use. The production of the cold kit and its labeling were validated, as were the radiochemical purity measurement and analytical procedures for determining the Na2EDTA dihydrate content in the kits. In this study, we validated a GMP kit for the simple production of [68Ga]Ga-EDTA, with the intention of applicability for human use.

Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [68Ga]Ga-DOTANOC and [68Ga]Ga-DATA5m-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [68Ga]Ga-DOTANOC & [68Ga]Ga-DATA5m-LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [68Ga]Ga-DATA5m-LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [68Ga]Ga-DOTANOC PET/CT (p < 0.0001). [68Ga]Ga-DATA5m-LM4 had statistical significance over [68Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p < 0.0001 (292 vs. 253 283 lesions on CT)] and bone metastases [100% vs. 82.9%; p = 0.005 (45 vs. 34 41 lesions on CT)]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [68Ga]Ga-DATA5m-LM4 showed better sensitivity and a higher target-to-background ratio than [68Ga]Ga-DOTANOC PET/CT. [68Ga]Ga-DATA5m-LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy.

For the positron emission tomography (PET) imaging of prostate cancer, radiotracers targeting the prostate-specific membrane antigen (PSMA) are nowadays used in clinical practice. Almost 10 years after its discovery, [68Ga]Ga-PSMA-11 has been approved in the United States by the Food and Drug Administration (FDA) as the first 68Ga-radiopharmaceutical for the PET imaging of PSMA-positive prostate cancer in 2020. This radiopharmaceutical combines the peptidomimetic Glu-NH-CO-NH-Lys(Ahx)-HBED-CC with the radionuclide 68Ga, enabling specific imaging of tumor cells expressing PSMA. Such a targeting approach may also be used for therapy planning as well as potentially for the evaluation of treatment response.

Small-molecule inhibitors targeting prostate-specific membrane antigen (PSMA) have demonstrated promising results in the theranostics of prostate cancer (PCa). We designed and synthesized a novel small-molecule PSMA inhibitor, SC691. This study aimed to conduct a preliminary clinical prospective investigation of 68 Ga-SC691. Following predefined inclusion/exclusion criteria, this study enrolled 7 healthy volunteers and 12 patients with PCa. Patients underwent 68 Ga-SC691 and 68 Ga-PSMA-11 PET/CT imaging within one week. PET/CT data were analyzed using a uWS-MI workstation. 68 Ga-SC691 demonstrated favorable safety profiles in all participants. 68 Ga-SC691 was primarily excreted via the urinary system, exhibiting a biodistribution similar to that of 68 Ga-PSMA-11. Compared to 68 Ga-PSMA-11, 68 Ga-SC691 showed lower non-specific organs uptake, particularly in the liver: 2.5 ± 0.7 vs. 4.1 ± 1.6 ( P  = 0.002). Furthermore, 68 Ga-SC691 and 68 Ga-PSMA-11 detected the same number and location of PSMA-positive lesions in PCa primary tumors, bone metastases, and lymph nodes metastases. Notably, 68 Ga-SC691 demonstrated higher tumor-to-non-tumor ratios (T/NT) ( P  < 0.05). In conclusions, as a novel small-molecule PSMA inhibitor, SC691 exhibits a favorable safety profile, biodistribution, and diagnostic performance, suggesting its potential as a valuable agent for PCa imaging and therapy. The lower non-specific organ uptake further supports its promise for theranostic applications.

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from 68Ge/68Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications.

BackgroundAlthough myocardial fibrosis can be quantified by magnetic resonance (MR), assessment of fibrosis activity is important as this will inform disease activity and the presence of ongoing adverse cardiac remodelling. Fibroblast activation protein (FAP) is expressed on the surface of activated myofibroblasts and is a marker of ongoing fibrosis activity. Radiolabelled FAP-specific ligands, such as 68-Gallium (68Ga)-FAP inhibitor (FAPI), represent a promising new approach to quantify fibrosis activity in the myocardium.PurposeTo investigate whether 68Ga-FAPI positron emission tomography (PET)/MR can detect myocardial fibrosis activity in patients with heart failure with reduced ejection fraction.MethodsIn a prospective cross-sectional study, patients with heart failure with reduced ejection fraction and healthy volunteers underwent 68Ga-FAPI PET/MR. 10 patients had repeat imaging at 6 months. Standardised uptake values (SUVmax) and tissue to background ratios (TBR) were calculated within the left ventricular (LV) wall.ResultsParticipants were predominantly middle-aged men: patients with heart failure (n=45; median age 65 [60-74] years, 76% male) and healthy volunteers (59 [56-62] years,70% male). LV ejection fraction was reduced in patients with heart failure (40±8%) but was normal in healthy volunteers (60±6%; P<0.001). Within the heart failure cohort, 22 patients had ischaemic cardiomyopathy and 23 patients had non-ischaemic cardiomyopathy. Compared with healthy volunteers, patients with heart failure had higher myocardial uptake of 68Ga-FAPI (SUVmax 3.2±1.5 versus 1.5±0.3, p<0.001; TBR 1.9±0.8 versus 1.1±0.2, p<0.001; Figure 1). Myocardial 68Ga-FAPI uptake was higher in patients with either ischaemic or non-ischaemic cardiomyopathy compared to healthy volunteers (SUVmax 4.0±1.7 and 2.3±0.5 versus 1.5±0.3 respectively; p<0.001 for both) and was higher in patients with ischaemic compared to non-ischaemic cardiomyopathy (p<0.001). Differential patterns of 68Ga-FAPI uptake were also observed with increased LV uptake seen particularly in the basal septum of patients with non-ischaemic cardiomyopathy and in the infarct zone of patients with ischaemic cardiomyopathy (Figure 2). Based on the Youden’s index of the receiver-operator curves, the optimal threshold for identifying myocardial fibrosis in patients with heart failure was SUVmax of 1.9 with a specificity of 90%, sensitivity of 89% and area under the curve of 0.94. At 6 months, 68Ga-FAPI uptake was unchanged in the 10 patients with chronic heart failure that underwent repeat scanning (p=0.91).ConclusionIncreased myocardial fibrosis activity can be detected with 68Ga-FAPI PET/MR in patients with heart failure. Differential patterns of 68Ga-FAPI uptake are seen in patients with non-ischaemic cardiomyopathy or ischaemic cardiomyopathy. This may help characterise and prognosticate patients with heart failure and inform the future development of novel heart failure therapies.Abstract 127 Figure 1Abstract 127 Figure 2Conflict of InterestNone

We report column material for a 68Ge/68Ga generator with acid resistance and excellent adsorption and desorption capacity of 68Ge and 68Ga, respectively. Despite being a core element of the 68Ge/68Ga generator system, research on this has been insufficient. Therefore, we synthesized a low molecular chitosan-based TiO2 (LC-TiO2) adsorbent via a physical trapping method as a durable 68Ge/68Ga generator column material. The adsorption/desorption studies exhibited a higher separation factor of 68Ge/68Ga in the concentration range of HCl examined (0.01 M to 1.0 M). The prepared LC-TiO2 adsorbent showed acid resistance capabilities with >93% of 68Ga elution yield and 1.6 × 10−4% of 68Ge breakthrough. In particular, the labeling efficiency of DOTA and NOTA, by using the generator eluted 68Ga, was quite encouraging and confirmed to be 99.65 and 99.69%, respectively. Accordingly, the resulting behavior of LC-TiO2 towards 68Ge/68Ga adsorption/desorption capacity and stability with aqueous HCl exhibited a high potential for ion-exchange solid-phase extraction for the 68Ge/68Ga generator column material.

Objective(s): The present work describes the automated radiochemical synthesis of different PET tracers like [68Ga]Ga-Pentixafor, [68Ga]Ga-FAPI-4 and [68Ga]Ga-DOTATATE using optimized single protocol in the non-cassette based Eckert & Ziegler (EZ) Modular Lab (fixed tubing system) without any modification in the inbuilt human machine interface (HMI) software. Recently, PET agents viz. [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4 are gaining prominence for the diagnosis of overexpressed Chemokine Receptor-4 (CXCR4) and Fibroblast Activation Protein (FAP) receptor, respectively, in the microenvironment of numerous cancer types. The promising results observed with the clinical usage of [68Ga]Ga-DOTATATE produced using the automated protocol, provided impetus for the clinical translation of [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4 using the in-house developed automated radiolabeling protocol.Methods:Herein we report a single radiolabeling protocol for the automated preparation of [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4 in the non-cassette based EZ Modular-Lab Standard radiochemistry module, without any changes in schematic, graphical user interface (GUI) software and time list, from that used for routine production of [68Ga]Ga-DOTATATE in our centre, since 2015. Physico-chemical quality control and in-vitro stability analyses were carried out using radio-TLC and radio-HPLC. Results: The automated protocol yielded reliable and consistent non-decay corrected (ndc) radiochemical yield (RCY) of (84.4%±0.9%) and (85.5%±1.4%) respectively, for [68Ga]Ga-Pentixafor and [68Ga]Ga-FAPI-4, with RCP>98%, which are comparable to the RCY of (84.4%±1.2%) and RCP (99.1%±0.3%) for [68Ga]Ga-DOTATATE. The biological quality control studies confirmed the formulations to be of ready-to-use pharmaceutical grade.Conclusion:The consistent and reliable RCY and RCP of multiple 68Ga-labeled PET tracers by single automated radiochemistry protocol exhibits the versatility of the EZ Modular Lab.