Development of a New 131I-Labelled Bisphosphonic Acid for Palliative Therapy ofMetastatic Bone-Pain

摘要

Approximately, 80% of all patients with cancer in advance stage could develop bonernmetastases. Isotopes used for pain palliation by bone metastases are very expensive, with exception ofrn32P, which could, however, cause bone-marrow depression. The aim of the present work was torndevelop a new bisphosphonic acid labeled with 131I for metastatic bone-pain palliation. Materials andrnmethods: An aryl-substituted bisphosphonic acid (PICIC-1), that would easily accept the 131I, wasrnsynthesized starting from DL-tyrosine. Its purity was tested by reverse-phase HPLC using a RP18rncolumn (4.6 mm x 100 mm) and a gradient from 0% to 100% of methanol in water as mobile phase.rnIts structure was analyzed by IR spectroscopy and by electrospray mass-spectrometry. Compound wasrnlabeled with 131I by using Chloramine-T method and then purify through AgCl filters. The stability ofrnthe label was assessed up to 72 h in PBS 0.05 M pH = 7.0-7.2 and HAS. Biodistribution was studied inrnmale Sprague Dawly rats (190-210g). Two hundred μCi of 131I-PICIC-1 (0.1 mg) were injected into arnlateral tail vein and blood samples and organs were removed at different times. Scintigraphic imagesrnof rats were performed. Results: Synthesized compound showed a chemical purity higher 97%.rnLabeling yield was higher 95%. Bone uptake was 1.2% of administered dose. Significant uptake wasrnobserved in kidneys and bowels, suggesting an excretion pathway by these organs. Skeleton of the ratrnwas visualized in scintigraphic images, with an uptake proportional to metabolic activity. Conclusions:rn131I-labeled-PICIC-1 showed satisfactory bone affinity and could be a promising newrnradiopharmaceutical for metastatic bone-pain palliation.