Evaluation of Intratumoral Injection of Poly(d,l-lactide) Cisplatin Microspheres in Rats with Breast Tumors Using [131I]lodomisonidazole (IMISO)

Abstract This study utilized [131I]iodomisonidazole (IMISO) to examine changes in tumor hypoxia after therapy of breast cancer with poly(d,l-lactide) cisplatin microspheres (PLA-CDDP MSs) by an intratumoral injection technique. PLA-CDDP MSs were prepared by a solvent evaporation process. Breast tumor cells were inoculated into the thighs of rats. After therapy with CDDP or PLA-CDDP MSs (6 mg/kg, subcutaneously, single injection), the tumor volume and blood chemistry of breast tumor-bearing rats were measured and compared daily with those of a control group given saline alone for 16 days. A group of rats were administered [131I]IMISO (50 μCi per rat, intravenously, n = 3) on day 5 and planar scintigraphy was then acquired at 2 h after injection. The percentage of tumor uptake (region of interest) was quantitated by a computer image analyzer and expressed as percentage of injected dose (ID) per pixel. PLA-CDDP microspheres (50-100 (Jim) contained 40.04% (w/w) cisplatin and produced sustained-release properties in vitro. The tumor volume decreased as a function of time after therapy with CDDP. The PLA-CDDP MS group had significantly less renal toxicity than the CDDP group. In rats treated with PLA-CDDP MS followed by [131I]IMISO, tumor %ID/pixel decreased 40% from 0.039 ± 0.001 to 0.024 ± 0.002. There was also a 40-50% decrease in tumor size after therapy with PLA-CDDP MSs. The results indicate that intratumoral injection of PLA-CDDP MSs can significantly reduce renal toxicity with the same therapeutic result as that of CDDP and its response could be monitored by [131I]IMISO.