[(99)mTc(CO)(3)]- Radiolabeled Bevacizumab: In vitro and in vivo Evaluation in a Melanoma Model

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Citações na Scopus
20
Tipo de produção
article
Data de publicação
2013
Editora
KARGER
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CAMACHO, Ximena
GARCIA, Maria Fernanda
CALZADA, Victoria
FERNANDEZ, Marcelo
CHABALGOITY, Jose A.
MORENO, Maria
ALONSO, Omar
GAMBINI, Juan Pablo
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ONCOLOGY, v.84, n.4, p.200-209, 2013
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Resumo
Introduction: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies. Objective: To radiolabel bevacizumab with [Tc-99m(CO)(3)(OH2)(3)]+ and evaluate it in vivo and in vitro for melanoma imaging properties. Methods: Bevacizumab was radiolabeled with [Tc-99m(CO)(3)(OH2)(3)]+ ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays. Results: We demonstrate that Tc-99m(CO)(3) -bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of Tc-99m(CO)(3)-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of Tc-99m(CO)(3)-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples. Conclusions: Tc-99m(CO)(3)-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy.
Palavras-chave
Preclinical imaging, Melanoma, Bevacizumab, Radiolabeling, Technetium-99m
Referências
  1. Akizawa H, 2008, ADV DRUG DELIVER REV, V60, P1319, DOI 10.1016/j.addr.2008.04.005
  2. Alberto R, 1999, COORDIN CHEM REV, V192, P901
  3. Alberto R, 1998, J AM CHEM SOC, V120, P7987, DOI 10.1021/ja980745t
  4. Alberto R, 2003, EUR J NUCL MED MOL I, V30, P1299, DOI 10.1007/s00259-003-1292-0
  5. Chen WJ, 2008, APPL RADIAT ISOTOPES, V66, P340, DOI 10.1016/j.apradiso.2007.09.007
  6. Ferlay J, 2004, GLOBOCAN 200I CANC I, P147
  7. Ferrara N, 1999, NAT MED, V15, P359
  8. Fidler IJ, 1999, CANCER CHEMOTH PHARM, V43, pS3, DOI 10.1007/s002800051091
  9. Fidler IJ, 1998, J DERMATOL SURG ONC, V14, P875
  10. Gotthardt M, 2007, J NUCL MED, V48, P596, DOI 10.2967/jnumed.106.036020
  11. Graells J, 2004, J INVEST DERMATOL, V123, P1151, DOI 10.1111/j.0022-202X.2004.23460.x
  12. Hurwitz H, 2004, NEW ENGL J MED, V350, P2335, DOI 10.1056/NEJMoa032691
  13. JURISSON S, 1993, CHEM REV, V93, P1137, DOI 10.1021/cr00019a013
  14. Kumar SR, 2007, CLIN CANCER RES, V13, P6070, DOI 10.1158/1078-0432.CCR-07-0160
  15. MONACCI WT, 1993, AM J PHYSIOL, V264, pC995
  16. Presta LG, 1997, CANCER RES, V57, P4593
  17. Redondo P, 2000, CYTOKINE, V12, P374, DOI 10.1006/cyto.1999.0566
  18. Riley LB, 2009, SURG CLIN N AM, V89, P1, DOI 10.1016/j.suc.2008.09.016
  19. ROGERS BE, 1995, CANCER RES, V55, pS5714
  20. Rosen LS, 2005, ONCOLOGIST, V10, P382, DOI 10.1634/theoncologist.10-6-382
  21. Schibli R., 2001, Journal of Labelled Compounds and Radiopharmaceuticals, V44, pS501
  22. Schibli R, 2002, EUR J NUCL MED MOL I, V29, P1529, DOI 10.1007/s00259-002-0900-8
  23. Soengas MS, 2003, ONCOGENE, V22, P3138, DOI 10.1038/sj.onc.1206454
  24. Stahl J, 2004, ISR MED ASSOC J, V6, P774
  25. Tsai SW, 2001, BIOCONJUGATE CHEM, V12, P264, DOI 10.1021/bc0000987
  26. Zhang XZ, 2007, APPL RADIAT ISOTOPES, V65, P287, DOI 10.1016/j.apradiso.2006.09.001