Targeting of the antivascular drug combretastatin to irradiated tumors results in tumor growth delay.
OBJECTIVE
The aim of the study is to evaluate the effects of targeting the antivascular drug combretastatin to irradiated mouse melanomas.


METHODS
Combretastatin was incorporated into liposomes with surfaces modified by the addition of cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD) to create an immunoliposome (IL). This addition of RGD allows the liposome to be preferentially targeted to alphavbeta3, an integrin up-regulated in the vasculature of irradiated tumors. C57BL mice bearing a transplanted B16-F10 melanoma were randomly assigned to one of the following treatment groups: untreated, a single dose of 5-Gy radiation (IR), IL (14.5 mg/kg of combretastatin), 5-Gy radiation plus IL, and a systemic administration of free drug (81.0 mg/kg of combretastatin).


RESULTS
In this transplanted tumor model, there was no significant increase in the volume of the IL + IR (5 Gy) treated tumors during the initial 6 days posttreatment; all other treatment groups exhibited exponential growth curves after day 3. The IL + IR (5 Gy) treatment resulted in a 5.1-day tumor growth delay compared to untreated controls.


CONCLUSIONS
These findings indicate that preferential targeting of antivascular drugs to irradiated tumors results in significant tumor growth delay.
Pattillo
Christopher B
CB
Department of Mechanical Engineering, Temple University, Philadelphia, Pennsylvania, USA.
Sari-Sarraf
Farid
F
Nallamothu
Ramakrishna
R
Moore
Bob M
BM
Wood
George C
GC
Kiani
Mohammad F
MF
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001632:Bibenzyls / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D008081:Liposomes; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013267:Stilbenes / Q000008:administration & dosage*; D047368:Tumor Burden
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D008081:Liposomes; D013267:Stilbenes; C040105:combretastatin