Abstract
Three different polyaminocarboxylate-based bifunctional NE3TA (7-[2-[carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) chelating agents were synthesized for potential use in copper 64-PET imaging applications. The bifunctional chelates were comparatively evaluated using transferrin (Tf) as a model targeting vector that binds to the transferrin receptor overexpressed in many different cancer cells. The transferrin conjugates of the NE3TA-based bifunctional chelates were evaluated for radiolabeling with 64Cu. In vitro stability and cellular uptake of 64Cu-radiolabeled conjugates were evaluated in human serum and prostate (PC-3) cancer cells, respectively. Among the three NE3TA-Tf conjugates tested, N-NE3TA-Tf was identified as the best conjugate for radiolabeling with 64Cu. N-NE3TA-Tf rapidly bound to 64Cu (> 98% radiolabeling efficiency, 1 min, RT), and 64Cu-N-NE3TA-Tf remained stable in human serum for 2 days and demonstrated high uptake in PC-3 cancer cells. 64Cu-N-NE3TA-Tf was shown to have rapid blood clearance and increasing tumor uptake in PC-3 tumor bearing mice over a 24 h period. This bifunctional chelate presents highly efficient chelation chemistry with 64Cu under mild condition that can be applied for radiolabeling of various tumor-specific biomolecules with 64Cu for potential use in PET imaging applications.
Original language | English |
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Pages (from-to) | 60-66 |
Number of pages | 7 |
Journal | Journal of Inorganic Biochemistry |
Volume | 154 |
DOIs | |
State | Published - Jan 2016 |
Keywords
- Bifunctional chelator
- Biodistribution
- Copper 64
- Radiolabeling
- Serum stability
- Transferrin