RT Journal Article
SR Electronic
T1 Monitoring Tumor Response to Antiangiogenic Sunitinib Therapy with <sup>18</sup>F-Fluciclatide, an <sup>18</sup>F-Labeled α<sub>V</sub>β<sub>3</sub>-Integrin and α<sub>V</sub>β<sub>5</sub>-Integrin Imaging Agent
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 424
OP 430
DO 10.2967/jnumed.110.077479
VO 52
IS 3
A1 Battle, Mark R.
A1 Goggi, Julian L.
A1 Allen, Lucy
A1 Barnett, Jon
A1 Morrison, Matthew S.
YR 2011
UL http://jnm.snmjournals.org/content/52/3/424.abstract
AB Arginine-glycine-aspartate (RGD)-binding αVβ3-integrin and αVβ5-integrin play key roles in tumor angiogenesis. We examined an 18F-labeled small peptide (fluciclatide [United States Adopted Name (ASAN)–approved, International Nonproprietary Name (INN)–proposed name], previously referred to as AH111585) containing an RGD sequence. Fluciclatide binds with a high (nM) affinity to αVβ3-integrin and αVβ5-integrin, which are highly expressed on tumors and the tumor neovasculature. In this study, 18F-fluciclatide was used to examine the response of human glioblastoma xenografts to treatment with the antiangiogenic agent sunitinib. Methods: U87-MG tumor uptake of 18F-fluciclatide was determined by small-animal PET after longitudinal administration of the antiangiogenic agent sunitinib (a 2-wk dosing regimen). Tumor sizes were measured throughout the study, and tumor volumes were calculated. Tumor microvessel density (MVD) after therapy was also analyzed. Results: Dynamic small-animal PET of 18F-fluciclatide uptake after administration of the clinically relevant antiangiogenic agent sunitinib revealed a reduction in the tumor uptake of 18F-fluciclatide compared with that in vehicle-treated controls over the 2-wk dosing regimen. Skeletal muscle, used as a reference tissue, showed equivalent 18F-fluciclatide uptake in both therapy and control groups. A reduction in tumor MVD was also observed after treatment with the antiangiogenic agent. No significant changes in tumor volume were observed in the 2 groups. Conclusion: The data demonstrated that 18F-fluciclatide detected changes in tumor uptake after acute antiangiogenic therapy markedly earlier than any significant volumetric changes were observable. These results suggest that this imaging agent may provide clinically important information for guiding patient care and monitoring the response to antiangiogenic therapy.