The Distribution Volume of 18 F-Albumin as a Potential Biomarker of Antiangiogenic Treatment Efficacy.

OBJECTIVE: 18 F-albumin, a vascular imaging agent, may have potential to assess tumor responses to anti-angiogenic therapies. In these studies tumor distribution volume of 18 F-albumin were first determined in various human tumor xenografts from biodistribtuion measurments and then one of the tumor type was used to evaluate changes in 18 F-albumin uptake in anti-angiognic tumor model.

METHOD: 18 F-albumin was synthesized via conjugation of 6-[18 F]fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [18 F]F-Py-TFP, with rat albumin. From the biodistribution of 18 F-albumin in various human tumor xenografts tumor distribution volumes (DVs; tumor%ID/g :blood%ID/g ) were first determined at various time points. Then, the ability of 18 F-albumin to detect tumor angiogenic inhibition in one of these tumor types (U87MG) following treatment with sunitinib was evaluated by position emission tomography (PET) imaging at 0, 7, 14, and 21 days post treatment. Caliper measurements of tumor dimensions were also made at these same times. At Day 21, following imaging, biodistributions, autoradiography of tumor tissues and tumor blood vessel counts (CD31 IHC) were performed.

RESULTS: 18 F-albumin retention in various tumors steadily increased over time with U87MG tumor exhibiting the highest uptake (DV) at all times. Significant decreases in 18 F-albumin DVs were observed one week post-treatement (-39%) vs. controls whereas tumor caliper volumes were not significantly decreased until days 14 and 21. At day 21 the significant decrease in DVs in the treatment group (-44%) paralleled biodistribution DV measurements and was consistent with autoradiography and CD31 IHC findings.

CONCLUSION: These data suggest that 18 F-albumin DVs obtained by imaging may serve as an early biomarker of the effectiveness of anti-angiogenic therapy and thus aid in patient management and treatment planning.