Labeling of DTPA-BP with Tc-99m and Ga-68 as new phosphorus bone imaging agents

1531 Objectives Radiolabeled bisphosphonates (Tc-99m MDP or HDP) have been used for nuclear bone scanning. The major existing disadvantage is slow clearance from soft tissue. In addition, both MDP and HDP bear no chelators and they tend to degrade with time and produce pertechnetate as an impurity. To overcome these disadvantages, we developed a chelator-based phosphorus imaging agent with fast clearance. This study was aimed to evaluate Tc-99m and Ga-68 labeled N6-carboxymethyl-N3,N9-bis[2,2-bis(phosphono)-2-hydroxy]ethyl-3,6,9-triazaundecanedioic acid (DTPA-BP) as new novel agents of bone imaging. Methods DTPA-BP was synthesized by reacting tris(trimethylsilyl) phosphite with DTPA anhydride followed by hydrolysis and purification by sephadex. DTPA-BP was labeled with Tc-99m/tin (II) chloride and Ga-68 chloride. Biodistribution of Tc-99m and Ga-68 DTPA-BP and Tc-99m MDP (reference standard) was studied in normal female F-344 rats. The bone metastases model was created by injecting human prostate cancer cells (PC-3, PC-118b) into the right femur of male athymic nude mice. Planar and PET imaging of Tc-99m and Ga-68 DTPA-BP (150 µCi/mouse, iv) were performed. Results The total yield of DTPA-BP was 10-15%. Radiochemical purity of Tc-99m and Ga-68 DTPA-BP (1mg) were >90%. The biodistribution in normal rats revealed bone-to-blood and bone-to-muscle count density ratios was ranged 1.8±0.79 to 21.5±3.40; 9.4±2.62 to 104.4±31.55 for Tc-99m at 0.5-4 hrs post-injection, and 3.4±0.80 to 5.3±0.24; 13.6±3.46 to 21.8±11.50 for Ga-68 DTPA-BP at 0.5-2 hrs post-injection, respectively. The uptakes of Tc-99m and Ga-68 DTPA-BP and Tc-99m MDP in bones (%ID/g) at 0.5 hr were 1.2±0.62, 2.2±0.45 and 1.8±0.31, respectively. The osteoblastic lesion was clearly visible at 30 min after injection of Tc-99m and Ga-68 DTPA-BP with soft tissue clearance. Conclusions Tc-99m and Ga-68 DTPA-BP exhibited high uptakes in normal bone and also osteoblastic metastasis of prostate cancer. They may be useful to stage prostate cancer and also monitor therapeutic response