RT Journal Article
SR Electronic
T1 18F-Peptide probe for PET imaging of VEGF expression
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1506
OP 1506
VO 51
IS supplement 2
A1 Marik, Jan
A1 Fedorova, Anna
A1 Zobel, Kerry
A1 Gill, Herman
A1 Ogasawara, Annie
A1 Tinianow, Jeff
A1 Murray, Jeremy
A1 Williams, Simon
A1 Deshayes, Kurt
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/1506.abstract
AB 1506 Objectives Blocking vascular endothelial growth factor (VEGF) has been validated as an effective approach for cancer therapy and overexpression of VEGF in tumors is associated with a poor prognosis. Recently, the anti-VEGF mAb bevacizumab was radiolabeled with 89Zr and used to monitor VEGF expression in human ovarian tumor xenografts using PET [1]. However, due to the long plasma half-life of radiolabeled bevacizumab, seven days are required to achieve maximum contrast. Additionally, since the VEGF levels may be rapidly changing, the use of 89Zr-mAbs may not be suitable for imaging of acute VEGF levels. Methods Since PET probes based on 18F-labeled peptides demonstrate fast clearance, optimal contrast can be achieved within a few hours allowing repeated daily imaging. Target specific 18F-peptides can be obtained by combinatorial drug discovery methods combined with high throughput PET [2]. Results Phage display library of peptides was screened against human VEGF and four peptides were identified with binding affinities to VEGF in the range 24-105 nM. The peptides were synthesized on solid phase and decorated with 4-pentynoic acid at the N-terminus, purified, and radiolabeled with 18F-PEG8-N3 using copper catalyzed alkyne-azide cycloaddition [3] with 21-45% RCY. The imaging properties of 18F-peptides were evaluated in human colon cancer model (HM7) and the peptide 18F-A3B provided the highest tumor uptake (0.85 ± 0.14 %ID/g, n = 3) with average tumor/blood and tumor/muscle ratios equal to 2.2 and 5.6 reached within 2 h post injection. The images obtained with 18F-A3B were comparable to images obtained using 89Zr-B20 (anti-VEGF mAb) and 89Zr-bevacizumab. Conclusions In conclusion, we have developed a peptide based 18F-tracer for non-invasive PET of VEGF expression. [1] Nagengast WB et al J. Nucl. Med. 2007, 48, 1313 [2] Gagnon MKJ et al PNAS 2009, 106, 17904 [3] Gill HS et al J. Med. Chem. 2009, 52, 581