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

Abstract

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.

• Authors: Bluma Linkowski Faintuch, Gustavo Eutimio Fernandez Núñez, Rodrigo Teodoro, Ana M Moro, Jair Mengatti
• Journal: Clinics (Sao Paulo, Brazil) (Clinics (Sao Paulo)) Vol. 66 Issue 2 Pg. 327-36 ( 2011) ISSN: 1980-5322 [Electronic] United States
• PMID: 21484054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Morpholines
• Organotechnetium Compounds
• Radioisotopes
• technetium 99m HYNIC-bombesin
• Streptavidin
• Bombesin

Topics

• Animals
• Bombesin (analogs & derivatives, metabolism)
• Cell Line, Tumor
• Chromatography, High Pressure Liquid (methods)
• Disease Models, Animal
• Male
• Mice
• Mice, Nude
• Molecular Imaging (methods)
• Morpholines (pharmacokinetics)
• Nanoparticles
• Organotechnetium Compounds
• Prostatic Neoplasms (diagnostic imaging, metabolism)
• Radioisotopes (chemistry)
• Radionuclide Imaging
• Random Allocation
• Streptavidin (pharmacokinetics)
• Time Factors