The effect of irradiation on the biodistribution of radiolabeled pegylated liposomes.
OBJECTIVE
The effect of total-body irradiation (TBI) on the biodistribution and pharmacokinetics of (111)In-DTPA-labeled pegylated liposomes (IDLPL) was evaluated in tumor-bearing nude mice as part of an ongoing effort to develop liposome-targeted radiosensitizers.


METHODS
Mice received 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 the effect of radiation at times ranging from 72 h to 1 h before liposome injection on tumor and normal tissue uptake of IDLPL at 24 h. Tumor and tissue/organ levels of liposome uptake were measured by dissection and quantitation in a gamma counter.


RESULTS
For most tissues (tumor, liver, kidney, lung, skin, heart, and central nervous system), irradiation did not alter IDLPL biodistribution. Splenic uptake appeared to be increased by TBI, but further analysis revealed that this effect was due to reduced splenic weight in irradiated mice. IDLPL uptake was increased in the small intestine, stomach, musculoskeletal system, female reproductive tract, and adrenal glands in irradiated mice.


CONCLUSIONS
These findings suggest that concomitant administration of liposomal radiosensitizers during radical radiotherapy is likely to be safe. However, caution should be exercised in situations in which significant volumes of small intestine or hemopoietic tissue will be irradiated.
Harrington
K J
KJ
ICRF Oncology Unit, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, UK. Harrington.Kevin@mayo.edu
Rowlinson-Busza
G
G
Syrigos
K N
KN
Uster
P S
PS
Vile
R G
RG
Peters
A M
AM
Stewart
J S
JS
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D007624:KB Cells; D008081:Liposomes / Q000493:pharmacokinetics / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution; D014916:Whole-Body Irradiation; D023041:Xenograft Model Antitumor Assays
D007205:Indium Radioisotopes; D008081:Liposomes; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D004369:Pentetic Acid