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.