18F labeling of a peptide for PET imaging of receptor-expressing tumors

Objectives A new F-18-labeling technology based on binding an aluminum-F-18 (ALF-18) complex to a chelate was recently tested using a NOTA-hapten-peptide in a pretargeting procedure. Here, this methodology was extended for labeling of a bombesin (BBN) peptide for PET imaging of gastrin-releasing peptide receptors expressed in a variety of cancers.

Methods IMP 468, [ligand-8-Aoc-BBN(7-14)NH₂] MH+1367, bound to PC-3 cells in vitro and its binding was blocked with BBN. IC₅₀-values were similar for IMP 468 and BBN. For labeling, F-18 was heated with AlCl₃ and IMP 468 for 15 min. After HPLC purification, ¹⁸F-IMP 468 was injected iv into two groups of male nude mice bearing sc PC3 prostate cancer xenografts. For blocking purposes, one of the groups was given 100 µg of BBN 18 min before ¹⁸F-IMP 468. Both groups were necropsied 1.5 h later.

Results The group given ¹⁸F-IMP 468 alone showed tumor targeting, 3.2 ± 0.86 %ID/g. The uptake in the small intestines and bone (scapula) were 24.6 ± 7.5 and 0.05 ± 0.03 %ID/g, respectively. When BBN was given before ¹⁸F-IMP 468, uptake in the tumor and small intestines was reduced to 1.05 ± 0.20 and 13.9 ± 3.0%ID/g, respectively. Bone uptake of F-18 was 5.7 ± 1.1 % ID/g and AlF-18 was 9.8 ± 2.3 ID/g). The low uptake of ¹⁸F-IMP 468 in the bone indicates in vivo stability and the absence of the possible breakdown products F-18 and AlF-18 for the duration of the study.

Conclusions AlF-18 can provide a convenient and rapid method for labeling peptides in PET imaging, including peptide receptors expressed in cancer.

Research Support In part by NIH/NIBIB Grant 1 R43 EB003751-01A1.