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

• DOI: 10.2967/jnumed.107.039487
• Publication Date: 2007-07-13T20:43:34Z
• Authors: J. C. Garrison; T. L. Rold; G. L. Sieckman; S. D. Figueroa; W. A. Volkert; S. S. Jurisson; T. J. Hoffman
• Keywords: DOTA; Radionuclide therapy

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