A comparative study of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor

Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, 188Re complexes with diastereomeric DMSA were prepared to compare the properties of 188Re(V)-rac-DMSA with those of 188Re(V)-meso-DMSA in in vitro and in vivo models. Methods: rac-2,3-DMSA was synthesized and radiolabeled with 188Re. The biodistribution and gamma camera imaging of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines. Results and conclusions: Both 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with 188Re(V)-meso-DMSA, 188Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. 188Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas 188Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of 188Re(V)-rac-DMSA was 3.5 times higher than that of 188Re(V)-meso-DMSA at 1 h (P<.01). Gamma camera images showed that 188Re(V)-rac-DMSA was more selectively localized than 188Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that 188Re(V)-rac-DMSA may have better potential than 188Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors