Evaluation of intratumoral injection of poly(d,l-lactide) cisplatin microspheres in rats with breast tumors using [¹³¹I]iodomisonidazole (IMISO)

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 (DD) per pixel. PLA-CDDP microspheres (50-100 μm) 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.