A HIGHLY SENSITIVE MODEL FOR QUANTIFICATION OF IN-VIVO TUMOR ANGIOGENESIS INDUCED BY ALGINATE-ENCAPSULATED TUMOR-CELLS

A remarkable approach to a specific tumor angiogenesis model in vivo i s the use of alginate implants encapsulating tumor cells. However, thi s previously reported approach has often been questioned because of do ubts regarding the relevance of hemoglobin at the alginate implant as a parameter of vascularization. In the present investigation, me exami ned whether or not the use of the blood pool agents FITC-dextran of hi gh molecular weight would significantly improve the determination of v ascularization at the alginate implant. In our experiments, we found a rapid distribution of FITC-dextran within the blood circulation of mi ce after i.v. bolus injection. The amount of FITC-dextran within algin ate implants strongly correlated with the number of LL2 carcinoma cell s or B16/F10 cells encapsulated. Even a low number of 10(3) cells per alginate implant led to a significantly increased accumulation of FITC -dextran. A more than 10-fold stimulation above that of controls was f ound with alginate implants containing 10(4) LL2 or B16/F10 tumor cell s. Using the investigational compound AGM-1470 in different treatment schedules, me found that quantification of alginate implant angiogenes is with FITC-dextran is a sensitive method for the determination of an giogenesis inhibition. In conclusion, our results demonstrated that th e use of FITC-dextran enables highly sensitive, quantitative measureme nt of blood vessel formation by alginate implants.