Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells

Autor(es)

Faintuch, Bluma Linkowski ^[1] ; Fernandez Nunez, Gustavo Eutimio ^[1] ; Teodoro, Rodrigo ^[1] ; Moro, Ana M. ^[1] ; Mengatti, Jair ^[1]

Afiliação do(s) autor(es)

^[1] IPEN CNEN SP, Ctr Radiofarm, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 66, n. 2, p. 327-336, 2011.
• Citações Web of Science: 4

Resumo

OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 %. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 %ID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile. (AU)

• Processo FAPESP: 07/57616-2 - Desenvolvimento de fármaco para diagnóstico cintilográfico de câncer pelo método da pré-marcação do tumor ('pretargeting') à base de morfolino conjugado a análogo da bombesina
• Beneficiário: Bluma Linkowski Faintuch
• Modalidade de apoio: Auxílio à Pesquisa - Regular