The effect of irradiation on the biodistribution of radiolabeled pegylatedliposomes

Purpose: The effect of total-body irradiation (TBI) on the biodistribution and pharmacokinetics of In-111-DTPA-labeled pegylated liposomes (IT)LPL) wa s evaluated in tumor-bearing nude mice as part of an ongoing effort to deve lop liposome-targeted radiosensitizers, Methods and Materials: Mice receive d TBI (2 Gy or 5 Gy) according to two protocols: (1) to test the effect of radiation delivered 30 min before liposome injection on the time course of IDLPL biodistribution to tumor and normal tissues over 96 h; (2) to test th e effect of radiation at times ranging from 72 h to 1 h before liposome inj ection on tumor and normal tissue uptake of IDLPL at 24 h, Tumor and tissue /organ levels of liposome uptake were measured by dissection and quantitati on in a gamma counter, Results: For most tissues (tumor, liver, kidney, lun g, skin, heart, and central nervous system), irradiation did not alter IDLP L biodistribution, Splenic uptake appeared to be increased by TBI, but furt her analysis revealed that this effect was due to reduced splenic weight in irradiated mice. IDLPL uptake was increased in the small intestine, stomac h, musculoskeletal system, female reproductive tract, and adrenal glands in irradiated mice. Conclusion: These findings suggest that concomitant admin istration of liposomal radiosensitizers during radical radiotherapy is like ly to be safe. However, caution should be exercised in situations in which significant volumes of small intestine or hemopoietic tissue will be irradi ated. (C) 2001 Elsevier Science Inc.