Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies

Pentavalent rhenium-188 dimercaptosuccinic acid [Re-188(V)DMSA] is a beta-emitting analogue of Tc-99m(V)DMSA, a tracer that is taken up in a variety of tumours and bone metastases. The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of Re-188 in mice was determined 2 h after injection of 3 MBq Re-188(V)DMSA prepared from eluate from a W-188/Re-188 generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases confirmed with a standard Tc-99m-hydroxymethylene diphosphonate (Tc-99m-HDP) scan, were given 370 MBq Re-188(V)DMSA and imaged at 3 h and 24 h using the 155-keV gamma-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of Re-188. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice,Re-188(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongly reminiscent of 99mTc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of Re-188 in any chemical form other than Re-188(V)DMSA up to 24 h. In conclusion, Re-188(V)DMSA and its Re-186 analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate Tc-99m(`V)DMSA.