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The aim of our work was to develop a generally applicable liquid chromatographic method for the determination of the residue free 68Ga3+ content of labeling reaction mixtures, in order to facilitate comparative labeling experiments in the early stages of chelator development. We achieved the retention of free 68Ga3+ on a mixed mode cation exchanger HPLC column with a gradient program, which allowed the separation from the non-retained complexes. The effects of reaction conditions (time, temperature) and the application of non-coordinating buffers were examined. Furthermore, recovery of free 68Ga3+ and these complexes were investigated, values of which were 94.9–97.4% and 87.4–99.6%. [ABSTRACT FROM AUTHOR]

Aluminum (Al) excess and hypercholesterinaemia are established risks of Alzheimer's disease (AD). The aim of this study was to establish an AD-resembling hypercholesterinaemic animal model—with the involvement of 8 week and 48 week-old Fischer-344 rats—by Al administration for the safe and rapid verification of β-amyloid-targeted positron emission tomography (PET) radiopharmaceuticals. Measurement of lipid parameters and β-amyloid–affine [11C]C-Pittsburgh Compound B ([11C]C-PIB) PET examinations were performed. Compared with the control, the significantly elevated cholesterol and LDL levels of the rats receiving the cholesterol-rich diet support the development of hypercholesterinaemia (p ≤ 0.01). In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young (p ≤ 0.05; p ≤ 0.01). A monotherapy-induced slight elevation of mean standardised uptake values (SUVmean) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUVmean increment compared to the adult control (SUVmean: from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [11C]C-PIB accumulation of AD-mimicking animals decreased by half and a third, respectively, to the baseline value. The proposed in vivo Al-induced AD-resembling animal system seems to be adequate for the understanding of AD neuropathology and future drug testing and radiopharmaceutical development. [ABSTRACT FROM AUTHOR]

Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer (PCa). Since bombesin analogue aminobenzoic-acid (AMBA) binds to GRPR with high affinity, scandium-44 conjugated AMBA is a promising radiotracer in the PET diagnostics of GRPR positive tumors. Herein, the GRPR specificity of the newly synthetized [44Sc]Sc-NODAGA-AMBA was investigated in vitro and in vivo applying PCa PC-3 xenograft. After the in-vitro assessment of receptor binding, PC-3 tumor-bearing mice were injected with [44Sc]Sc/[68Ga]Ga-NODAGA-AMBA (in blocking studies with bombesin) and in-vivo PET examinations were performed to determine the radiotracer uptake in standardized uptake values (SUV). 44Sc/68Ga-labelled NODAGA-AMBA was produced with high molar activity (approx. 20 GBq/µmoL) and excellent radiochemical purity. The in-vitro accumulation of [44Sc]Sc-NODAGA-AMBA in PC-3 cells was approximately 25-fold higher than that of the control HaCaT cells. Relatively higher uptake was found in vitro, ex vivo, and in vivo in the same tumor with the 44Sc-labelled probe compared to [68Ga]Ga-NODAGA-AMBA. The GRPR specificity of [44Sc]Sc-NODAGA-AMBA was confirmed by significantly (p ≤ 0.01) decreased %ID and SUV values in PC-3 tumors after bombesin pretreatment. The outstanding binding properties of the novel [44Sc]Sc-NODAGA-AMBA to GRPR outlines its potential to be a valuable radiotracer in the imaging of GRPR-positive PCa. [ABSTRACT FROM AUTHOR]

The goal of this work was to present two high-performance liquid chromatography (HPLC) method that could be applied for the determination of the total radioactive purity of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET). The separation of [18F]fluoride ions, [18F]FET and [18F]FET intermediate was accomplished on LiChrosper RP-18, 250 × 4 mm, 5 µm (Merck) analytical column. For mobile phase 10 mM potassium dihydrogen phosphate buffer at pH7 (A) and acetonitrile (B) was used: 0–2 min: 15% B; 2–12 min: 85% B; 12–15 min: 15% B, respectively. Analysis of [18F]FDG was performed using LiChrosper 100 NH2, 250 × 4.5 mm, 5 µm (Merck) analytical column. The initial mobile phase composition was 10 mM KH2PO4 buffer (pH7) and acetonitrile (15:85, v/v) and the acetonitrile ratio was decreased to 15% at 2 min after the sample injection and held for 5 min. Complete elution of [18F]fluoride ions from stationary phases could be achieved by adding 10 mg/mL K[19F]F to radioactive samples in a ratio 1:1 during the sample preparation. Recovery of [18F]fluoride ions ranged from 99.5 to 100.6%. The validation of the developed methods showed good results for linearity (r2 = 0.9981–0.9996), specificity (RS = 3.7–10.2), repeatability (%Area RSD% = 1.2–4.3%) and limit of quantitation (LOQ = 1.6–4.5 kBq). During the cross-validation similar radiochemical purity values were obtained by the novel HPLC methods and thin layer chromatography performed according to the recommendations of the Ph. Eur. monographs. [ABSTRACT FROM AUTHOR]

Background/aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled ( 52 Mn) randomly methylated beta-cyclodextrin ([ 52 Mn]Mn-DOTAGA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [ 68 Ga]Ga-DOTA-NAPamide and PGE2 selective [ 68 Ga]Ga-DOTAGA-RAMEB cyclodextrin., Materials and Methods: Post-injection of [ 68 Ga]Ga-DOTA-NAPamide, [ 68 Ga]Ga-DOTAGA-RAMEB, and [ 52 Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter., Results: Although all tracers performed well in tumor identification, the highest standardized uptake values were detected in the [ 68 Ga]Ga-DOTA-NAPamide scans. Corresponding to the ex vivo data, meaningful [ 52 Mn]Mn-DOTAGA-RAMEB accumulation 1 h post-injection confirmed the tumor-targeting potential of the tracer. Temporal changes in PGE2/EP2 expression of the neoplasms may explain the significant differences observed between the tumor uptake of the two cyclodextrin probes and that of the 52 Mn-labelled compound measured 1 h, 4 h, and 3 days post-injection (p≤0.01, p≤0.05)., Conclusion: Although further pharmacokinetical optimization may be required, 52 Mn-labelled cyclodextrin holds potential in melanoma diagnostics and the PET-based longitudinal assessment of tumor-associated PGE2/EP2 expression., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Formation and growth of metastases require a new vascular network. Angiogenesis plays an essential role in the expansion and progression of most malignancies. A high number of molecular pathways regulate angiogenesis, including vascular endothelial growth factor (VEGF), α v β 3 integrin, matrix metalloproteinases (MMPs), or aminopeptidase N. The aim of this study is to involve new, easily accessible peptide sequences into the of neo-angiogenesis in malignant processes. Labelling of these peptide ligands with 68 Ga enable PET imaging of neo-vascularization., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aminopeptidase N (APN/CD13) plays an important role in neoangiogenic process in malignancies. Our previous studies have already shown that 68 Ga-labelled NOTA conjugated asparagine-glycine-arginine peptide (c[KNGRE]-NH 2 ) specifically bind to APN/CD13 expressing tumors. The aim of this study was to evaluate and compare the APN/CD13 specificity of newly synthesized 68 Ga-labelled NGR derivatives in vivo by PET/MRI imaging using hepatocellular carcinoma (He/De) and mesoblastic nephroma (Ne/De) tumor models. PET/MRI and ex vivo biodistribution studies were performed 11 ± 1 days after subcutaneous injection of tumor cells and 90 min after intravenous injection of 68 Ga-NOTA-c(NGR), 68 Ga-NODAGA-c(NGR), 68 Ga-NODAGA-c(NGR) (MG1) or 68 Ga-NODAGA-c(NGR) (MG2). The APN/CD13 selectivity was confirmed by blocking experiments and the APN/CD13 expression was verified by immunohistochemistry. 68 Ga-labelled c(NGR) derivatives were produced with high specific activity and radiochemical purity. In control animals, low radiotracer accumulation was found in abdominal and thoracic organs. Using tumor-bearing animals we found that the 68 Ga-NOTA-c(NGR), 68 Ga-NODAGA-c(NGR), and 68 Ga-NODAGA-c(NGR) (MG1) derivatives showed higher uptake in He/De and Ne/De tumors, than that of the accumulation of 68 Ga-NODAGA-c(NGR) (MG2). APN/CD13 is a very promising target in PET imaging, however, the selection of the appropriate 68 Ga-labelled NGR-based radiopharmaceutical is critical for the precise detection of tumor neo-angiogenesis and for monitoring the efficacy of anticancer therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)