MicroPET imaging of tumor angiogenesis and monitoring on antiangiogenic therapy with an 18F labeled RGD-based probe in SKOV-3 xenograft-bearing mice
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So far, there is no satisfactory imaging modality to monitor antiangiogenesis therapy of ovarian cancer noninvasively. The aim of this study was to evaluate the effectiveness and sensibility of an 18F labeled Arg-Gly-Asp (RGD) peptide in imaging and monitoring antiangiogenic responds in SKOV-3 xenograft-bearing mice. 18F-FB-NH-PEG4-E[PEG4-c(RGDfK)]2 (denoted as 18F-RGD2) was synthesized and employed in this study. Mice bearing ovarian cancer SKOV-3 tumors were used for biodistribution and microPET imaging studies compared with 18F-FDG imaging. Animals were treated with low-dose paclitaxel and the effect of paclitaxel therapy on 18F-RGD2 accumulation was investigated. Microvascular density (MVD) of SKOV-3 tumors was detected to assess the reliability of 18F-RGD2 in antiangiogenesis monitoring. Biodistribution studies for 18F-RGD2 revealed favorable in vivo pharmacokinetic properties, with significant levels of receptor-specific tumor uptake determined via blocking studies. MicroPET imaging results demonstrated high contrast visualization of SKOV-3 tumors. And tumor to background ratio (T/NT) of 18F-RGD2 uptake was significantly higher than that of 18F-FDG. Studies on antiangiogenic therapy demonstrated percentage of injected dose per gram of tissue (%ID/g) tumor uptake of 18F-RGD2 which was obviously decreased in the treatment group than the control group, especially at 60 min (by 31.31 ± 7.18 %, P = 0.009) and 120 min (by 38.92 ± 8.31 %, P < 0.001) after injection of 18F-RGD2. MVD measurement of SKOV-3 tumors confirmed the finding of the biodistribution studies in monitoring antiangiogenesis therapy. 18F-RGD2, with favorable biodistribution properties and specific affinity, is a promising tracer for tumor imaging and monitoring antiangiogenesis therapy in ovarian cancer SKOV-3 xenograft-bearing mice.
KeywordsOvarian cancer Monitoring antiangiogenic therapy Target imaging RGD peptide Integrin imaging
This work was supported by grants from the National Natural Science Foundation of China No. 81071172. The authors would like to thank Nanjing PET-Tracer Co., Ltd (Nanjing, Jiangsu, China) for the assistance with radiosynthesis of 18F-RGD2.
- 1.Ferlay J, Soerjomataram I, Ervik M, Forman D, Bray F. GLOBOCAN, GLOBOCAN. Cancer incidence and mortality worldwide; 2012. http://globocan.iarc.fr.
- 3.Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N. SEER Cancer Statistics Review, 1975–2010, National Cancer Institute. Bethesda, MD, 2014; http://seer.cancer.gov/csr/1975_2010/.
- 6.Kumar R, Knick VB, Rudolph SK, Johnson JH, Crosby RM, Crouthamel MC, et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther. 2007;6:2012–21.CrossRefPubMedGoogle Scholar
- 7.Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30:2039–45.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Jin ZH, Furukawa T, Claron M, Boturyn D, Coll JL, Fukumura T, et al. Positron emission tomography imaging of tumor angiogenesis and monitoring of antiangiogenic efficacy using the novel tetrameric peptide probe 64Cu-cyclam-RAFT-c(−RGDfK-)4. Angiogenesis. 2012;15:569–80.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Aten E. Efficacy study of [F-18]RGD-K5 positron emission tomography (PET) as a tool to monitor response to an anti-angiogenic drug (K5-101). ClinicalTrials.gov; 2009.Google Scholar
- 29.Winick J. A proof-of-concept study to assess the ability of [18F]AH-111585 PET imaging to detect tumours and angiogenesis. ClinicalTrials.gov; 2007.Google Scholar
- 30.Kyung Moon W. PET-MR for prediction and monitoring of response to neoadjuvant chemotherapy in breast cancer. ClinicalTrials.gov; 2010.Google Scholar
- 31.Gleeson F. RGD-PET-CT in cancer angiogenesis. ClinicalTrials.gov; 2011.Google Scholar
- 32.Gambhir S. 18F FPPRGD2 positron emission tomography/computed tomography in predicting early response in patients with cancer receiving anti-angiogenesis therapy. ClinicalTrials.gov; 2013.Google Scholar