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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

Authors
 Jun-Young Park  ;  Tae-Sup Lee  ;  Tae-Hyun Choi  ;  Gi-Jeong Cheon  ;  Chang-Woon Choi  ;  Ok-Doo Awh 
Citation
 NUCLEAR MEDICINE AND BIOLOGY, Vol.34(8) : 1029-1036, 2007 
Journal Title
 NUCLEAR MEDICINE AND BIOLOGY 
ISSN
 0969-8051 
Issue Date
2007
MeSH
Animals ; Cell Line ; Female ; Isotope Labeling ; Metabolic Clearance Rate ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Organ Specificity ; Organometallic Compounds/pharmacokinetics* ; Organometallic Compounds/therapeutic use ; Pheochromocytoma/diagnostic imaging ; Pheochromocytoma/metabolism* ; Pheochromocytoma/radiotherapy ; Radionuclide Imaging ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/pharmacokinetics ; Radiopharmaceuticals/therapeutic use ; Rats ; Succimer/pharmacokinetics* ; Succimer/therapeutic use ; Tissue Distribution
Abstract
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. 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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0969805107001783
DOI
10.1016/j.nucmedbio.2007.06.016
Appears in Collections:
7. Others (기타) > Gangnam Severance Hospital (강남세브란스병원) > 1. Journal Papers
Yonsei Authors
Park, Jun Young(박준영) ORCID logo https://orcid.org/0000-0003-3403-2767
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170141
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