Synthesis, biodistribution and imaging properties of indium-111-DTPA-paclitaxel in mice bearing mammary tumors

Paclitaxel, an antineoplastic agent that stabilizes microtubules and arrests cells in the G2/M cell cycle phase, has shown activity against many common cancers, including ovarian and breast tumors. In order to evaluate the potential value of radiolabeled paclitaxel as an imaging tool in tumors, we synthesized ¹¹¹In-DTPA-paclitaxel and investigated its biodistribution and gamma scintigraphic imaging properties. Methods: Mice bearing a paclitaxel-responsive mammary tumor (MCA-4) were used. DTPA-paclitaxel was labeled with ¹¹¹ In with a radiochemical yield of 84% and radiochemical purity of 90%. Each mouse received 5 μCi of radiotracers intravenously for biodistribution studies and 100 μCi for gamma scintigraphic studies. Indium-111-DTPA was used as a control. Results: In tumor-bearing mice, ¹¹¹In-DTPA was characterized by rapid clearance from the plasma with negligible retention in the tumor, the liver and other body parts. In contrast, ¹¹¹In-DTPA-paclitaxel exhibited a pharmacological profile resembling that of paclitaxel. Furthermore, a significant uptake of ¹¹¹In-DTPA-paclitaxel was observed in the tumor. The tumor-to-muscle ratios were 2.64, 3.16 and 6.94 at 30 min, 2 hr and 24 hr, respectively, although absolute uptake in the tumor decreased from 1.95% (injected dose/g) at 30 min to 0.21 % at 24 hr after injection. The tumor-to-blood ratio reached 50 at 24 hr after injection. Gamma scintigraphy and autoradiographic studies clearly showed the retention of radiolabeled paclitaxel in the tumor 24 hr after injection. Conclusion: These studies suggest that ¹¹¹In-DTPA-paclitaxel may be clinically useful in studying the uptake of paclitaxel in solid tumors.