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, (188)Re 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.


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.
Park
Jun-Young
JY
Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju 220-710, South Korea.
Lee
Tae-Sup
TS
Choi
Tae-Hyun
TH
Cheon
Gi-Jeong
GJ
Choi
Chang-Woon
CW
Awh
Ok-Doo
OD
D000818:Animals; D002460:Cell Line; D005260:Female; D007553:Isotope Labeling; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010673:Pheochromocytoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D004113:Succimer / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C069609:rhenium(V)dimercaptosuccinic acid; D004113:Succimer