99mTc-Labeled Bevacizumab via HYNIC for Imaging of Melanoma

Authors

  • Ximena Camacho Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay
  • María Fernanda García Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay , Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay
  • Victoria Calzada Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay
  • Marcelo Fernandez Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay
  • Omar Alonso Centro de Medicina Nuclear, Hospital de Clínicas “Dr. Manuel Quintela”, Facultad de Medicina, Universidad de la República, Av. Italia s/n, 11600, Montevideo, Uruguay
  • Juan Pablo Gambini Centro de Medicina Nuclear, Hospital de Clínicas “Dr. Manuel Quintela”, Facultad de Medicina, Universidad de la República, Av. Italia s/n, 11600, Montevideo, Uruguay
  • Rodrigo Barbosa de Aguiar Laboratório de Oncologia Experimental, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo Nº 455- Cerqueira César - CEP: 01246903, São Paulo, Brazil
  • Camila Maria Longo Machado Nuclear Medicine Medical Investigation Laboratory LIM43-Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo - HCFMUSP, Brazil
  • Roger Chammas Laboratório de Oncologia Experimental, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo Nº 455- Cerqueira César - CEP: 01246903, São Paulo, Brazil
  • Williams Porcal Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay
  • Pablo Cabral Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay

DOI:

https://doi.org/10.6000/1927-7229.2014.03.01.9

Keywords:

Melanoma, Angiogenesis, Bevacizumab, HYNIC, organic synthesis, technetium-99m.

Abstract

 Vascular endothelial growth factor (VEGF) is one of the classic factors to tumour-induced angiogenesis in several types, including melanoma. Bevacizumab, a monoclonal antibody anti-VEGF, could be used as an imaging tool in clinical studies. The aim of this study was to radiolabeled Bevacizumab with 99mTc and evaluate it in vivoimaging properties. Bevacizumab was derivatized with the activated ester succinimidyl-hydrazinonicotinamide hydrochloride (Suc-HYNIC) as a bifunctional coupling agent. A mixture of Tricine/SnCl2.2H2O was added to Bevacizumab-HYNIC and radiolabeled with 99mTcO4-. The radiochemical stability of the radiolabeled sntibody was assessed. Biodistribution studies and SPECT-CT imaging were evaluated in healthy and tumor-bearing C57BL/6J mice at 1, 4 and 24 h (n =5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable over 24 h in solution and serum. In vivo biodistribution studies revealed tumor-to-muscle ratios of 99mTc-HYNIC-Bevacizumab was 9.28, 17.19 and 8.51 at 1, 4 and 24 h p.i. SPECT/CT imaging of tumor-bearing C57BL/6J mice showed tumor selective uptake of 99mTc-HYNIC-Bevacizumab. 99mTc-HYNIC-Bevacizumab could become a potential radiopharmaceutical to evaluate the expression of vascular endothelial growth factor (VEGF) in solid tumors and could be seen as a clinic tool for the screening of solid tumors that might respond to the Bevacizumab chemotherapy.

References

Folkman J. Tumor Angiogenesis; therapeutics implications. N Engl J Med 1971; 285: 1182-86. http://dx.doi.org/10.1056/NEJM197111182852108

Folkman J. Angiogenic factors. Science 1987; 235: 442-47. http://dx.doi.org/10.1126/science.2432664

Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990; 82: 4-6. http://dx.doi.org/10.1093/jnci/82.1.4

Dvorak HF. Angiogenesis. J Thromb Haemost 2005; 3: 1835-42. http://dx.doi.org/10.1111/j.1538-7836.2005.01361.x

Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005; 438: 932-36. http://dx.doi.org/10.1038/nature04478

Shibuya M. Stucture and fuction of VEGF/VEGF-receptor system involved in angiogenesis. Cell Sturct Funct 2001; 26: 25-35. http://dx.doi.org/10.1247/csf.26.25

Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999; 77: 527-43. http://dx.doi.org/10.1007/s001099900019

Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001; 280: 1358-66.

Ferrara N. Role of vascular endothelial growth factor in physiologic angiogenesis: therapeutic implications. Semin Oncol 2002; 29: 10-14.

Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25: 581-11. http://dx.doi.org/10.1210/er.2003-0027

Ferrara N, Davis-Smyth T. The biology of Vascular endothlial growth factor. Endocrine Rev 2008; 18: 4-25. http://dx.doi.org/10.1210/edrv.18.1.0287

Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other desease. Nat Med 1995; 1: 27-31. http://dx.doi.org/10.1038/nm0195-27

Ferrara N, Gerber HP, Le Couter J. The biology of VEGF and its receptors. Natl Med 2003; 9(6): 669-76. http://dx.doi.org/10.1038/nm0603-669

Hoeben A, Landuyt B, Highley M, Wildier H, Van Oosterom A, De Bruijn E. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004; 56: 549-80. http://dx.doi.org/10.1124/pr.56.4.3

Veikkola T, Karkkainen M, Cleasson-Welsh L, Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res 2000; 60: 203-12.

Shibuya M. Vascular endothelial growth factor receptor-2: its unique signaling and specific ligand, VEGF-E. Cancer Sci 2003; 94: 751-6. http://dx.doi.org/10.1111/j.1349-7006.2003.tb01514.x

Crawford SE. Vascular interference: a blockade to tumor epithelial growth. Hepatology 2004; 39: 1491-4. http://dx.doi.org/10.1002/hep.20278

Park JE, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 1993; 4: 1317-26. http://dx.doi.org/10.1091/mbc.4.12.1317

Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. Am Soc Clin Oncol 2002; 20: 4368-80. http://dx.doi.org/10.1200/JCO.2002.10.088

Rosen LS. VEGF-targeted therapy: terapeutics potential and recent advances. Oncologist 2005; 10: 382-91. http://dx.doi.org/10.1634/theoncologist.10-6-382

Gerber HP, Ferrara N. Pharmacology and pharmacody-namics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 2005; 65: 671-80.

Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, et al. Humanization of an anti- vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997; 57: 4593-99.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastic colorectal cancer. N Engl J Med 2004; 350: 2335-42. http://dx.doi.org/10.1056/NEJMoa032691

Stahl J, Bar-Meir E, Friedman E, Regev E, Orenstein A, Winkler E. Genetics in melanoma. Isr Med Assoc J 2004; 6: 774-7.

Gorski DH, Leal AD, Goydos JS. Differential expression of vascular endothelial growth factor-A isoforms at different stages of melanoma progression. J Am Coll Surg 2003; 197: 408-18. http://dx.doi.org/10.1016/S1072-7515(03)00388-0

Tas F, Duranyildiz D, Oguz H, Camlica H, Yasasever, Topuz E. Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients. Melanoma Res 2006; 16: 405-11. http://dx.doi.org/10.1097/01.cmr.0000222598.27438.82

Ferlay J, Parkin F, Pisani P, Parkin DM. Globocan 2002: Cancer Incidence, Mortality and Prevalence Worldwide. Lyon: IARC 2004; 147.

Sekulic A, Haluska P Jr, Miller AJ, Genebriera De Lamo J, Ejadi S, Paulido JS, et al. Malignant melanoma in the 21st century: the emerging molecular landscape. Mayo Clin Proc 2008; 83: 825-46. http://dx.doi.org/10.4065/83.7.825

Fidler IJ. The biology of melanoma metastasis. J Dermatol Surg Oncol 1998; 14: 875-81. http://dx.doi.org/10.1111/j.1524-4725.1988.tb03591.x

Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Oncol 2006; 3: 24-40. http://dx.doi.org/10.1038/ncponc0403

Nagengast WB, Vries EG, Hospers GA, Mulder NH, Jong JR, Hollem H, et al. In vivo VEGF imaging with radiolabeled Bevacizumab in a human ovarian tumor xenograft. J Nucl Med 2007; 48: 1313-19. http://dx.doi.org/10.2967/jnumed.107.041301

Stollman TH, Scheer MG, Leenders WP, Verrijp KC, Soede AC, Oyen WJ, et al. Specific imaging of VEGF-A expression with radiolabelled anti-VEGF monoclonal antibody. Int J Cancer 2008; 122: 2310-4. http://dx.doi.org/10.1002/ijc.23404

Stollman TH, Scheer MG, Franssen GM, Verrijp KC, Soede AC, Oyen WJ, et al. Tumor accumulation of radiolabelled bevacizumab due to targeting of cell- and matrix-associated VEGF-A isoforms. Cancer Biother Radiopharm 2009; 24: 195-200. http://dx.doi.org/10.1089/cbr.2008.0574

Chang SK, Rizvi I, Solban N, Hasan T. In vivo optical molecular imaging of vascular endothelial growth factor for monitoring cancer treatment. Clin Cancer Res 2008; 14: 4146-53. http://dx.doi.org/10.1158/1078-0432.CCR-07-4536

Scheer MG, Stollman TH, Boerman OC, Verrijp K, Sweep FC, Leenders WP, et al. Imaging liver metastases of colorectal cancer patients with radiolabelled bevacizumab: lack of correlation with VEGF-A expression. Eur J Cancer 2008; 44: 1835-40. http://dx.doi.org/10.1016/j.ejca.2008.05.026

Jurisson S, Berning D, Jia W, Ma D. Coordination Compounds in Nuclear Medicine. Chem Rev 1993; 93: 1137-56. http://dx.doi.org/10.1021/cr00019a013

Rennen HJ, Boerman OC, Koenders EB, Oyen WJ, Corstens FH. Labeling proteins with Tc-99m via Hydrazinonicotinamide (HYNIC): Optimization of the conjugation reaction. Nucl Med Biol 2000; 27: 599-604. http://dx.doi.org/10.1016/S0969-8051(00)00134-7

Meszaros LK, Dose A, Biagini SCG, Blower PJ. Hydrazinonicotinic acid (HYNIC)-Coordination chemistry and applications in radiopharmaceutical chemistry. Inorg Chim Acta 2010; 363: 1059-69. http://dx.doi.org/10.1016/j.ica.2010.01.009

Hantowich DJ, Virzi F, Forgarasi M, Rusckowski M, Winnard P. Can a Cysteine Challenge Assay Predict the In vivo Behavior of 99mTc-labeled Antibodies? Nuc Med Biol 1994; 21: 1035-44. http://dx.doi.org/10.1016/0969-8051(94)90175-9

Loening AM, Gambhir SS. AMIDE: A Free Software Tool for Multimodality Medical Image Analysis. Mol Imag 2003; 2(3): 131-37. http://dx.doi.org/10.1162/153535003322556877

Camacho X, García MF, Calzada V, Fernández M, Moreno M, De Aguiar R, et al.

Abrams MJ, Juweid M, tenKate CI, Schwartz DA, Hauser MM, Gaul FE, et al. Technetium-99m-Human Polyclonal IgG Radiolabeled via the Hydrazino Nicotinamide Derivatives for Imaging Focal Sites of Infection in Rats. J Nuc Med 1990; 31: 2022-18.

Camacho X, García MF, Calzada V, Fernández M, Porcal W, Alonso O, et al. Synthesis and evaluation of 99mTc chelate-conjugated Bevacizumab. Curr Radiopharm 2013; 6: 12-19. http://dx.doi.org/10.2174/1874471011306010003

Gotthardt M, van Eerd-Vismale J, Oyen WJ, de Jong M, Zhang H, Rolleman E, et al. Indication for different mechanisms of kidney uptake of radiolabeled peptides. J Nucl Med 2007; 48: 596-601. http://dx.doi.org/10.2967/jnumed.106.036020

Akizawa H, Uehara T, Arano Y. Renal uptake and metabolism of radiopharmaceuticals derived from peptides and proteins. Adv Drug Deliv Rev 2008; 60: 1319-28. http://dx.doi.org/10.1016/j.addr.2008.04.005

Tsai SW, Li L, Williams LE, Anderson AL, Raubitscheck AA, Shively JE. Metabolism and renal clearance of 111In-labeled DOTA-conjugated antibody fragments. Bioconjug Chem 2001; 12: 264-70. http://dx.doi.org/10.1021/bc0000987

Rogers BE, Franano FN, Duncan JR, Edwarda WB, Anderson CJ, Connett JM, Welch MJ. Identification of metabolites of 111In-diethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo. Cancer Res 1995; 55: 5714s-20s.

Kumar SR, Quinn TP, Deutscher SL. Evaluation of an 111In-radiolabeled peptide as a targeting and imaging agent for Erb-2 receptor expressing breast carcinomas. Clin Cancer Res 2007; 13: 6070-9. http://dx.doi.org/10.1158/1078-0432.CCR-07-0160

Monacci WT, Merrill MJ, Oldfield EH. Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 1993; 264(4 Pt 1): C995-1002.

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Published

2014-01-15

How to Cite

Ximena Camacho, María Fernanda García, Victoria Calzada, Marcelo Fernandez, Omar Alonso, Juan Pablo Gambini, Rodrigo Barbosa de Aguiar, Camila Maria Longo Machado, Roger Chammas, Williams Porcal, & Pablo Cabral. (2014). 99mTc-Labeled Bevacizumab via HYNIC for Imaging of Melanoma. Journal of Analytical Oncology, 3(1),  53–64. https://doi.org/10.6000/1927-7229.2014.03.01.9

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