Preparation and in vivo evaluation of 90Y-meso-dimercaptosuccinic acid (90Y-DMSA) for possible therapeutic use: comparison with 99mTc-DMSA.
BACKGROUND
The aim of this study was to find out if (90)Y could form a stabile complex with meso-2,3-dimercaptosuccinic acid (DMSA) and if (90)Y-DMSA may have potential for tumor therapy in the palliative treatment of bone metastases.


METHODS
The preparing of (90)Y-DMSA was carried out by varying experimental parameters, such as ligand concentration, pH, time, and temperature of the reaction, in order to maximize the labeling yield. Analysis of the complexes enclosed the radiochemical quality control (instant thin-layer chromatography, paper chromatography, and high-performance liquid chromatography), determination of pharmacokinetical parameters as well as biodistribution study in healthy male Wistar rats. In vitro stability of the complexes was tested too.


RESULTS
(90)Y-DMSA could be prepared in high yields (>95%) under optimized conditions of reaction. Stability studies in saline and human serum in vitro showed no significant release of activity from the ligand over 24 hours and 10 days, respectively. The preliminary biodistribution results in rat at 2 hours indicated that (90)Y-DMSA, at both pH levels, was significantly retained into bone. The uptake in the kidneys was lower for (90)Y-DMSA at pH 8.0 then at pH 3.0. The retention in other organs was negligible.


CONCLUSIONS
(90)Y complexes could be made with ease with DMSA. (90)Y-DMSA was obtained in good yield and was found to be very stable. A promising biodistribution result of this complex pointed at potential in the palliative treatment of bone metastases.
Djokić
Divna
D
Laboratory for Radioisotopes, The Institute of Nuclear Sciences Vinca, M. Petrovica Alasa 12-14, Belgrade, Serbia. djokici@vin.bg.ac.yu
Janković
Drilia
D
Nikolić
Nadezda
N
D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008297:Male; D009362:Neoplasm Metastasis; D010166:Palliative Care; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry; D013053:Spectrophotometry / Q000379:methods; D004113:Succimer / Q000138:chemical synthesis* / Q000627:therapeutic use*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000138:chemical synthesis* / Q000627:therapeutic use*; D015019:Yttrium / Q000627:therapeutic use*
D008024:Ligands; D012709:Serum Albumin; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D015019:Yttrium; D004113:Succimer