Evaluation Of Intratumoral Injection Of Poly(D,L-Lactide) Cisplatin Microspheres In Rats With Breast Tumors Using [I-131]Iodomisonidazole (Imiso)

This study utilized [I-131]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 mere measured and compared daily with those of a control group given saline alone for 16 days, A group of rats were administered [I-131]IMISO (50 mu Ci 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 mu m) 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 [I-131]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 [I-131]IMISO.