In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: Side-by-side comparison of the CB-TE2A and DOTA chelation systems

144Citations
Citations of this article
45Readers
Mendeley users who have this article in their library.

Abstract

The BB2 receptor subtype, of the bombesin family of receptors, has been shown to be highly overexpressed in a variety of human tumors, including prostate cancer. Bombesin (BBN), a 14-amino acid peptide, has been shown to target the BB2 receptor with high affinity. 64Cu (half-life = 12.7 h, β+: 18%, Eβ+max = 653 keV; β-: 37%, Eβ-max = 578 keV) is a radioisotope that has clinical potential for application in both diagnostic imaging and radionuclide therapy. Recently, new chelation systems such as 1,4,8,11-tetraazabicyclo[6.6.2] hexadecane-4,11-diacetic acid (CB-TE2A) have been reported to significantly stabilize the 64Cu radiometal in vivo. The increased stability of the 64Cu-CB-TE2A chelate complex has been shown to significantly reduce nontarget retention compared with tetraazamacrocycles such as 1,4,7,10-tetraazacyclodoadecane-N,N′,N″,N‴-tetraacetic acid (DOTA). The aim of this study was to determine whether the CB-TE2A chelation system could significantly improve the in vivo stability of 64Cu bombesin analogs. The study directly compares 64Cu bombesin analogs using the CB-TE2A and DOTA chelation systems in a prostate cancer xenograft SCID (severely compromised immunodeficient) mouse model. Methods: The CB-TE2A-8-AOC-BBN(7-14)NH2 and DOTA-8-AOC-BBN(7-14) NH2 conjugates were synthesized and radiolabeled with 64Cu. The receptor-binding affinity and internalization profile of each metallated conjugate was evaluated using PC-3 cells. Pharmacokinetic and small-animal PET/CT studies were performed using female SCID mice bearing PC-3 xenografts. Results: In vivo BB2 receptor targeting was confirmed by tumor uptake values of 6.95 ± 2.27 and 4.95 ± 0.91 %ID/g (percentage injected dose per gram) at the 15-min time point for the 64Cu-CB-TE2A and 64Cu-DOTA radioconjugates, respectively. At the 24-h time point, liver uptake was substantially reduced for the 64Cu-CB-TE2A radioconjugate (0.21 ± 0.06 %ID/g) compared with the 64Cu-DOTA radioconjugate (7.80 ± 1.51 %ID/g). The 64Cu-CB-TE2A-8-AOC- BBN(7-14)NH2 radioconjugate demonstrated significant clearance, 98.60 ± 0.28 %ID, from the mouse at 24 h after injection. In contrast, only 67.84 ± 5.43 %ID of the 64Cu activity was excreted using the 64Cu-DOTA-8-AOC-BBN(7-14)NH2 radioconjugate because of nontarget retention. Conclusion: The pharmacokinetic and small-animal PET/CT studies demonstrate significantly improved nontarget tissue clearance for the 64Cu-CB-TE2A8-AOC-BBN(7-14)NH2. This is attributed to the improved in vivo stability of the 64Cu-CB-TE2A chelate complex as compared with the 64Cu-DOTA chelate complex. Copyright © 2007 by the Society of Nuclear Medicine, Inc.

Cite

CITATION STYLE

APA

Garrison, J. C., Rold, T. L., Sieckman, G. L., Figueroa, S. D., Volkert, W. A., Jurisson, S. S., & Hoffman, T. J. (2007). In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: Side-by-side comparison of the CB-TE2A and DOTA chelation systems. Journal of Nuclear Medicine, 48(8), 1327–1337. https://doi.org/10.2967/jnumed.107.039487

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free