In vivo characterization of 68Ga-NOTA-VEGF121 for the imaging of VEGF receptor expression in U87MG tumor xenograft models

• Published in: European journal of nuclear medicine and molecular imaging 2013, Vol.40 (2), p.198-206
• Main Authors: Kang, Choong Mo, Kim, Sung-Min, Koo, Hyun-Jung, Yim, Min Su, Lee, Kyung-Han, Ryu, Eun Kyoung, Choe, Yearn Seong
• Format: Article
• Language: English
• Subjects: Cardiology; Imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Original Article; Orthopedics; Radiology
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-012-2266-x

Purpose Vascular endothelial growth factor receptors (VEGFRs) are associated with tumor growth and induction of tumor angiogenesis and are known to be overexpressed in various human tumors. In the present study, we prepared and evaluated 68 Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-benzyl (NOTA)-VEGF 121 as a positron emission tomography (PET) radioligand for the in vivo imaging of VEGFR expression. Methods 68 Ga-NOTA-VEGF 121 was prepared by conjugation of VEGF 121 and p -SCN-NOTA, followed by radiolabeling with 68 GaCl 3 and then purification using a PD-10 column. Human aortic endothelial cell (HAEC) binding of 68 Ga-NOTA-VEGF 121 was measured as a function of time. MicroPET and biodistribution studies of U87MG tumor xenografted mice were performed at 1, 2, and 4 h after injection of 68 Ga-NOTA-VEGF 121 . The tumor tissues were then sectioned and subjected to immunostaining. Results The decay-corrected radiochemical yield of 68 Ga-NOTA-VEGF 121 was 40 ± 4.5 % and specific activity was 243.1 ± 104.6 GBq/μmol (8.6 ± 3.7 GBq/mg). 68 Ga-NOTA-VEGF 121 was avidly taken up by HAECs in a time-dependent manner, and the uptake was blocked either by 32 % with VEGF 121 or by 49 % with VEGFR2 antibody at 4 h post-incubation. In microPET images of U87MG tumor xenografted mice, radioactivity was accumulated in tumors (2.73±0.32 %ID/g at 2 h), and the uptake was blocked by 40 % in the presence of VEGF 121 . In biodistribution studies, tumor uptake (1.84±0.14 %ID/g at 2 h) was blocked with VEGF 121 at a similar level (52 %) to that of microPET images. Immunostaining analysis of U87MG tumor tissues obtained after the microPET imaging showed high levels of VEGFR2 expression. Conclusion These results demonstrate that 68 Ga-NOTA-VEGF 121 has potential for the in vivo imaging of VEGFR expression. In addition, our results also suggest that the in vivo characteristics of radiolabeled VEGF depend on the properties of the radioisotope and the chelator used.