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

2011; Elsevier BV; Volume: 66; Issue: 2 Linguagem: Inglês

10.1590/s1807-59322011000200024

1980-5322

Bluma Linkowski Faintuch, Eutímio Gustavo Fernández Núñez, Rodrigo Teodoro, Ana Maria Moro, Jair Mengatti,

Prostate Cancer Treatment and Research

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. A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (β-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. 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-βAla-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. 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.