This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Collingridge, D. R. Articles by Harris, A. L. Search for Related Content PubMed PubMed Citation Articles by Collingridge, D. R. Articles by Harris, A. L.

The Development of [¹²⁴I]Iodinated-VG76e

A Novel Tracer for Imaging Vascular Endothelial Growth Factor in Vivo Using Positron Emission Tomography¹

Cancer Research UK Positron Emission Tomography Oncology Group, Department of Cancer Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0NN [D. R. C., E. O. A., O. C. H., H. B., P. P.]; Imperial Cancer Research Fund Molecular Oncology Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DF [V.A.C., R.B., A.L.H.]; and Imaging Research Solutions Limited, Hammersmith Hospital, London W12 0NN [M.G., S.O., S.K.L., F.B.], United Kingdom

The development of anticancer therapies that target the angiogenic process is an area of major growth in oncology. A method of noninvasively measuring tumor vascular endothelial growth factor (VEGF) in vivo could provide important efficacy information for VEGF-dependent antiangiogenic agents and the role of VEGF in cancer biology. We have developed a novel radiotracer for use with positron emission tomography (PET) that enables noninvasive imaging of VEGF. This radiotracer comprises an IgG1 monoclonal antibody, known as VG76e, that binds to human VEGF, labeled with a positron-emitting radionuclide, iodine-124 ([¹²⁴I]-SHPP-VG76e). Three radiolabeling strategies were evaluated to synthesize the radiotracer with optimal radiochemical yield, purity, and immunoreactivity. To evaluate the pharmacokinetics and VEGF-specific localization of [¹²⁴I]-SHPP-VG76e, two subclones of the HT1080 human fibrosarcoma selected on the basis of differing VEGF production (26.6 and 1/3C, the former producing 2–4-fold more in vitro) were established in culture and grown as solid tumor xenografts in immune-deficient mice. A single i.v. injection of the radiotracer into tumor-bearing mice revealed a time dependent and specific localization of [¹²⁵I]-SHPP-VG76e to the tumor tissue. Three validation studies established the VEGF specificity and potential for use of [¹²⁴I]-SHPP-VG76e in vivo: (a) uptake of [¹²⁵I]-SHPP-VG76e was 1.8-fold higher in HT1080–26.6 compared with HT1080–1/3C tumors (P < 0.05); (b) uptake of [¹²⁵I]-SHPP-VG76e in HT1080–26.6 tumors was specifically blocked by prior administration of excess unlabeled VG76e (P < 0.05); and (c) tumor uptake of the IgG1, [¹²⁵I]-SHPP-CIP5, which has a similar molecular weight as [¹²⁵I]-SHPP-VG76e but does not recognize VEGF, was the same for both HT1080–26.6 and HT1080–1/3C (P > 0.05). Other than tumor localization, [¹²⁵I]-SHPP-VG76e was present in urine and blood and to a lesser extent in heart, lungs, liver, kidney, and spleen. Whole-animal PET imaging studies revealed a high tumor-to-background contrast and also revealed [¹²⁴I]-SHPP-VG76e distributions in the major organs. These studies support further development of [¹²⁴I]-SHPP-VG76e as a radiotracer for measuring tumor levels of VEGF in humans.

This article has been cited by other articles:

				T. E. Peterson and H. C. Manning Molecular Imaging: 18F-FDG PET and a Whole Lot More J. Nucl. Med. Technol., September 1, 2009; 37(3): 151 - 161. [Abstract] [Full Text] [PDF]

				L. W. Dobrucki, D. P. Dione, L. Kalinowski, D. Dione, M. Mendizabal, J. Yu, X. Papademetris, W. C. Sessa, and A. J. Sinusas Serial Noninvasive Targeted Imaging of Peripheral Angiogenesis: Validation and Application of a Semiautomated Quantitative Approach J. Nucl. Med., August 1, 2009; 50(8): 1356 - 1363. [Abstract] [Full Text] [PDF]

				W. Cai and X. Chen Multimodality Molecular Imaging of Tumor Angiogenesis J. Nucl. Med., June 1, 2008; 49(Suppl_2): 113S - 128S. [Abstract] [Full Text] [PDF]

				D. S. Boss, R. V. Olmos, M. Sinaasappel, J. H. Beijnen, and J. H. M. Schellens Application of PET/CT in the Development of Novel Anticancer Drugs Oncologist, January 1, 2008; 13(1): 25 - 38. [Abstract] [Full Text] [PDF]

				G. A.M.S. van Dongen, G. W.M. Visser, M. N. Lub-de Hooge, E. G. de Vries, and L. R. Perk Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications Oncologist, December 1, 2007; 12(12): 1379 - 1389. [Abstract] [Full Text] [PDF]

				W. B. Nagengast, E. G. de Vries, G. A. Hospers, N. H. Mulder, J. R. de Jong, H. Hollema, A. H. Brouwers, G. A. van Dongen, L. R. Perk, and M. N. Lub-de Hooge In Vivo VEGF Imaging with Radiolabeled Bevacizumab in a Human Ovarian Tumor Xenograft J. Nucl. Med., August 1, 2007; 48(8): 1313 - 1319. [Abstract] [Full Text] [PDF]

				R. Rossin, D. Berndorff, M. Friebe, L. M. Dinkelborg, and M. J. Welch Small-Animal PET of Tumor Angiogenesis Using a 76Br-Labeled Human Recombinant Antibody Fragment to the ED-B Domain of Fibronectin J. Nucl. Med., July 1, 2007; 48(7): 1172 - 1179. [Abstract] [Full Text] [PDF]

				A. R. Hsu, W. Cai, A. Veeravagu, K. A. Mohamedali, K. Chen, S. Kim, H. Vogel, L. C. Hou, V. Tse, M. G. Rosenblum, et al. Multimodality Molecular Imaging of Glioblastoma Growth Inhibition with Vasculature-Targeting Fusion Toxin VEGF121/rGel J. Nucl. Med., March 1, 2007; 48(3): 445 - 454. [Abstract] [Full Text] [PDF]

				J. M. Provenzale Imaging of Angiogenesis: Clinical Techniques and Novel Imaging Methods Am. J. Roentgenol., January 1, 2007; 188(1): 11 - 23. [Abstract] [Full Text] [PDF]

				W. Cai, K. Chen, K. A. Mohamedali, Q. Cao, S. S. Gambhir, M. G. Rosenblum, and X. Chen PET of Vascular Endothelial Growth Factor Receptor Expression J. Nucl. Med., December 1, 2006; 47(12): 2048 - 2056. [Abstract] [Full Text] [PDF]

				W. Cai, J. Rao, S. S. Gambhir, and X. Chen How molecular imaging is speeding up antiangiogenic drug development. Mol. Cancer Ther., November 1, 2006; 5(11): 2624 - 2633. [Abstract] [Full Text] [PDF]

				M. Lubberink, A. van Schie, H. W.A.M. de Jong, G. A.M.S. van Dongen, and G. J.J. Teule Acquisition Settings for PET of 124I Administered Simultaneously with Therapeutic Amounts of 131I J. Nucl. Med., August 1, 2006; 47(8): 1375 - 1381. [Abstract] [Full Text] [PDF]

				P. Workman, E. O. Aboagye, Y.-L. Chung, J. R. Griffiths, R. Hart, M. O. Leach, R. J. Maxwell, P. M. J. McSheehy, P. M. Price, and J. Zweit Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. J Natl Cancer Inst, May 3, 2006; 98(9): 580 - 598. [Abstract] [Full Text] [PDF]

				C. Chan, J. Sandhu, A. Guha, D. A. Scollard, J. Wang, P. Chen, K. Bai, L. Lee, and R. M. Reilly A Human Transferrin-Vascular Endothelial Growth Factor (hnTf-VEGF) Fusion Protein Containing an Integrated Binding Site for 111In for Imaging Tumor Angiogenesis J. Nucl. Med., October 1, 2005; 46(10): 1745 - 1752. [Abstract] [Full Text] [PDF]

				M. Jain and S. K. Batra Genetically Engineered Antibody Fragments and PET Imaging: A New Era of Radioimmunodiagnosis J. Nucl. Med., December 1, 2003; 44(12): 1970 - 1972. [Full Text] [PDF]

				G M Tozer Measuring tumour vascular response to antivascular and antiangiogenic drugs Br. J. Radiol., December 1, 2003; 76(suppl_1): S23 - S35. [Abstract] [Full Text] [PDF]

				G R Laking and P M Price Positron emission tomographic imaging of angiogenesis and vascular function Br. J. Radiol., December 1, 2003; 76(suppl_1): S50 - S59. [Abstract] [Full Text] [PDF]

				S M Galbraith Antivascular cancer treatments: imaging biomarkers in pharmaceutical drug development Br. J. Radiol., December 1, 2003; 76(suppl_1): S83 - S86. [Full Text] [PDF]