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Abstract: 99mTc-technetium (99mTc) and 188Re-rhenium (188Re) represent an interesting pair of radionuclides for diagnosis and therapy. The aim of this study was to synthesize and characterize in vitro/in vivo the first 188Re-folate derivative [188Re(CO)3–picolylamine monoacetic acid 188Re-PAMA-folate (2)] for potential targeted radionuclide therapy of FR-positive tumors. The data were compared with those of the isostructural 99mTc-analog [99mTc–PAMA folate (1)] reported previously. Methods: In vitro stability of compound 2 was tested in phosphate-buffered saline and human plasma. Cell binding experiments were performed with FR-positive human KB cells. Biodistribution was assessed in female nude mice, bearing KB tumor xenografts. Results: Cell binding experiments showed high and FR-specific uptake. In vivo, compound 2 accumulated specifically in the FR-positive tumors with maximal values 4 h post injection (p.i.) [ 2 : 1.87±0.04 percent injected dose per gram of weight tissue (% ID/g) vs. 1 : 2.33±0.36% ID/g]. Unfavorably high retention of radioactivity was found in FR-positive kidneys (12.04±0.62% ID/g; 4 h p.i.). Tumor-to-blood ratio of radioactivity ( 2 : 14.5±1.32, 4 h p.i.) was lower than for compound 1 (58.0±12.2, 4 h p.i.), whereas tumor-to-kidney ratios were in the same range ( 2 : 0.15±0.01 vs. 1 : 0.13±0.02, 4 h p.i.). Preadministration of the antifolate pemetrexed significantly improved the tumor-to-kidney ratio ( 2 : 1.59±0.30, 4 h p.i.). Conclusions: The isostructural radiofolates 1 and 2 displayed almost identical pharmacokinetic profiles and accumulated both specifically in FR-positive tumors. However, only the coapplication of the antifolate pemetrexed improved the biodistribution of the radiotracers in such ways that a potential therapeutic application of compound 2 can be envisaged in the future. [Copyright &y& Elsevier]

Abstract: The first purely chemical method for automated no-carrier-added synthesis of [1-11C]-labeled d(R)- and l(S)-2-hydroxypropanoic acid (lactic acid) was developed for experimental neurophysiology studies and position emission tomography (PET) diagnosis. Starting from sodium 1-hydroxyethanesulfonate and [11C]HCN (trapped as [11C]KCN) the intermediate dl-(R,S)-[1-11C]-2-hydroxypropanenitrile was prepared. Its rapid acid hydrolysis gave dl-(R,S)-[1-11C]lactic acid, which was isolated by preparative reversed phase HPLC and automatically injected on a second preparative C18 HPLC column coated with a chiral selector, where both [1-11C]lactic acid enantiomers were separated by chiral ligand-exchange chromatography. Two novel chiral selectors for HPLC enantiomeric separation of α-hydroxy acids, namely d(R)- or l(S)-2-amino-3-methyl-3-(5-phenylpentylsulfanyl)-butanoic acid were utilized for the preparative HPLC separation of the [1-11C]lactic acid enantiomers. The preparation of the selectors and the coating procedure for the manufacturing of the preparative chiral HPLC columns are described. A highly efficient trap for [11C]HCN is presented. The whole radiosynthesis is automated, takes about 45min and leads to more than 80% decay corrected overall radiochemical yield of each enantiomer (up to 2.5GBq) with over 99% radiochemical, chemical and enantiomeric purity. The specific activity at the end of the synthesis is about 400GBq/μmol. [Copyright &y& Elsevier]

Purpose: For the assessment of folate-based radiopharmaceuticals, human nasopharyngeal KB carcinoma cells are traditionally used although nasopharyngeal cancer is rare. On the other hand, the folate receptor (FR) is frequently overexpressed on diverse cancer types, the highest frequency (>90%) being on ovarian carcinomas. The goal of our study was the in vitro and in vivo assessment of different FR-positive human carcinoma cells. In addition, a murine sarcoma cell line was assessed as a pre-clinical alternative to human xenograft models. Methods: FR-positive human nasopharyngeal, cervical, ovarian and colorectal cancer cell lines and the transgenic mouse sarcoma (24JK-FBP) cell line were targeted with a novel 99mTc-tricarbonyl folate derivative 2. Comparative in vitro cell binding studies were carried out under standardised folate-deficient conditions. In vivo studies were performed in nude mice and C6 black mice. Results: The in vitro cell experiments revealed only FR-specific binding (unspecific <0.02%), ranging from 3.5% to 52% of complex 2 owing to variable levels of FR expression of the cell lines. In vivo tumour uptake of radiotracer 2 varied less than in vitro. It ranged from 0.66± 0.17% ID/g (LoVo) through 1.16±0.64% ID/g (IGROV-1) and 1.55±0.43% ID/g (24JK-FBP) to 2.33±0.36% ID/g (KB) 4 h p.i. Conclusion: These pre-clinical studies indicate that in vitro data obtained in FR-positive cancer cells do not necessarily correspond with or predict in vivo radiofolate uptake in corresponding (xeno)grafts. In addition, the murine 24JK-FBP cell line proved to be a valuable preclinical alternative to human tumour models. [ABSTRACT FROM AUTHOR]

Tracer technology makes it possible to observe physiological and biochemical processes in the living organism in a dynamic mode. Positron emission tomography adds the use of chemically unchanged biomolecules and of quantification. This opens up fascinating possibilities for both fundamental research and routine diagnostic applications. [ABSTRACT FROM AUTHOR]

Highlights from the article: This special issue of I Journal of Labelled Compounds and Radiopharmaceuticals i is dedicated to the outstanding work of Prof Dr habil. Jörg has organized several international meetings, including the recent 22nd International Symposium on Radiopharmaceutical Sciences (ISRS) 2017 in Dresden, and he has served in many functions, always with the aim of advancing the radiopharmaceutical sciences. He has participated in IAEA programmes concerned with training staff and installing radiopharmaceutical production units in developing countries and he has been very active in the Certified European Postgraduate Course for Radiopharmaceutical Chemistry and Pharmacy at the ETH in Zurich.

Studies the imaging of renal carcinoma xenografts with copper-lebelled anti-L1-CAM antibody chCE7. Uptake of subcutaneous tumor xenografts.