RT Journal Article
SR Electronic
T1 PET of Vascular Endothelial Growth Factor Receptor Expression
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 2048
OP 2056
VO 47
IS 12
A1 Weibo Cai
A1 Kai Chen
A1 Khalid A. Mohamedali
A1 Qizhen Cao
A1 Sanjiv S. Gambhir
A1 Michael G. Rosenblum
A1 Xiaoyuan Chen
YR 2006
UL http://jnm.snmjournals.org/content/47/12/2048.abstract
AB For solid tumors and metastatic lesions, tumor vascularity is a critical factor in assessing response to therapy. Here we report the first example, to our knowledge, of 64Cu-labeled vascular endothelial growth factor 121 (VEGF121) for PET of VEGF receptor (VEGFR) expression in vivo. Methods: VEGF121 was conjugated with 1,4,7,10-tetraazadodecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA) and then labeled with 64Cu for small-animal PET of mice bearing different sized U87MG human glioblastoma xenografts. Blocking experiments and ex vivo histopathology were performed to confirm the in vivo results. Results: There were 4.3 ± 0.2 DOTA molecules per VEGF121, and the VEGFR2 binding affinity of DOTA-VEGF121 was comparable to VEGF121. 64Cu labeling of DOTA-VEGF121 was achieved in 90 ± 10 min and the radiolabeling yield was 87.4% ± 3.2%. The specific activity of 64Cu-DOTA-VEGF121 was 3.2 ± 0.1 GBq/mg with a radiochemical purity of >98%. Small-animal PET revealed rapid, specific, and prominent uptake of 64Cu-DOTA-VEGF121 in small U87MG tumors (high VEGFR2 expression) but significantly lower and sporadic uptake in large U87MG tumors (low VEGFR2 expression). No appreciable renal clearance of 64Cu-DOTA-VEGF121 was observed, although the kidney uptake was relatively high likely due to VEGFR1 expression. Blocking experiments, immunofluorescence staining, and western blot confirmed the VEGFR specificity of 64Cu-DOTA-VEGF121. Conclusion: Successful demonstration of the ability of 64Cu-DOTA-VEGF121 to visualize VEGFR expression in vivo may allow for clinical translation of this radiopharmaceutical for imaging tumor angiogenesis and guiding antiangiogenic treatment, especially patient selection and treatment monitoring of VEGFR-targeted cancer therapy.