Preparation and biodistribution of 2-(5-[18F]fluoro-pentyl)-2-methyl-malonic acid and its clinical application

Abstract

Objective To synthesize 2-(5-[18F]fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) and to investigate the biodistribution in mice and the primary clinical application. Methods 18F-ML-10 was synthesized by domestic synthesis module MF-2V-IT-1. Quality control of the probe was performed after automated synthesis. The biological characteristics of 18F-ML-10 were assessed by biodistribution assay on male Kunming mice and microPET imaging on a male SD rat. Six patients with brain metastasis (4 males, 2 females, and age 21-68 years) were enrolled in this study. 18F-ML-10 PET images were acquired before and at 48 h after radiotherapy. SUVmean and SUVmax of ROI were calculated. GTV changes were measured by MRI before and 3 months after radiotherapy. Response of brain metastasis to radiotherapy was assessed by PET imaging with 18F-ML-10. Two-sample t test was used. Results The non-corrected radiochemical yield of 18F-ML-10 was (26.5±7.3)% with acceptable quality. The radiochemical purity exceeded 99%. 18F-ML-10 was excreted through the kidneys, and the radiouptake in the blood was declined rapidly. The radiotracer accumulation was low in most of other organs. The testis showed a significant uptake. The SUVmean and SUVmax after radiotherapy (5.54±2.72 and 7.29±3.09) were significantly higher than the baseline values(3.81±1.13 and 4.97±1.05; t=2.670, 2.663, both P<0.05). The GTV after radiotherapy was significantly lower than the baseline value: (13.14±9.39) cm3vs (23.34±18.13) cm3;t=3.002, P<0.05. Conclusions 18F-ML-10 could be synthesized reliably and repeatedly by domestic synthesis module. It has satisfactory properties in vivo and is probably suitable for early assessment of the response to radiotherapy in patients with brain metastasis. Key words: Methylmalonic acid; Isotope labeling; Fluorine radioisotopes; Tomography, emission-computed; Neoplasm metastasis; Brain