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Radiopharmaceutical Chemistry: New Chemistry-OncologyNew Chemistry-Oncology I: Peptides |
1 Immunomedics, Inc., Morris Plains, New Jersey; 2 Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey
384
Objectives: To develop a simple, rapid, and stable method of labeling peptides and proteins with F-18. The F-18 labeled peptide could then be used for pretargeted immunoPET, and other applications.
Methods: F-18 was initially bound with diverse metals, such as Al, Be, Co, Fe, Ga, In, Lu, Y, and Zn in order to be chelated to a peptide via a ligand. Various ligands tested included EDTA, NTA, DTPA, DOTA, and NOTA.
Results: F-18 was combined initially with the DTPA-containing peptide, IMP-272 (DTPA-QAK(HSG)YdK(HSG)-NH2), using HSG (histamine-succinyl-glycine) as the peptide hapten because of its being the target of the second arm of the bispecific antibody (bsMAb). Among the metals used, Al was found to be preferred, because the aluminum fluoride bond is stable in vivo, and permitted labeling with F-18 at up to 96% yield forming a single major peak by HPLC. However, since DTPA-Al-F-18 was not stable in serum, a NOTA peptide (IMP-449) was then prepared: NOTA-benzyl-ITC-AdKd(HSG)YdKd(HSG)-NH2. After labeling with Al-F-18, this peptide was stable in serum for 4 h at 37 degrees centigrade. Using IMP-449 conjugated with F-18, we are evaluating pretargeted ImmunoPET imaging with a trivalent anti-CEA x anti-HSG bsMAb.
Conclusions: By means of a NOTA complex with aluminum-F-18, a simple and rapid method of labeling peptides and proteins with F-18 has been developed, and is being used for bsMAb pretargeting ImmunoPET.
Research Support: Supported in part by NIH/NIBIB grant R43 EB003751-01.
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