The radiochemical yield for 18F-alakyne folate was 22%. Mice inoculated with human KB cancer cells were intravenously injected with 18F-DBCO folate and 18F-alakyne folate. Both folate derivatives demonstrated stability in human serum albumin and high affinity for the folate receptor. However, 18F-DBCO folate was more lipophilic than 18F-alakyne folate, which resulted in a greater degree of non-specific binding. The in vivo performance was consequently higher for 18F-alakyne folate, giving much clearer visualization of folate receptor-positive tumours in PET scans7. There was lower tumour-to-liver contrast than expected due to accumulation of 18F-alakyne folate in the liver and gal bladder.
In view of high radiochemical yield, radiochemical purity and favourable pharmacokinetics, 18F-alakyne folate is expected to be a promising candidate for folate receptor PET imaging. However, there remains the need to fine-tune the metabolism profile of 18F-alakyne folate.
References
1. Teng L, et al. Clinical translation of folate receptor-targeted therapeutics. Expert Opin Drug Deliv. 2012;9(8):901‑908.
2. Muller C, Schibli R. Folic acid conjugates for nuclear imaging of folate receptor-positive cancer. J Nucl Med 2011;52:1-4.
3. Kim MH, et al. Synthesis and Evaluation of 99mTc-Labeled Folate-Tripeptide Conjugate as a Folate Receptor-Targeted Imaging Agent in a Tumor-Bearing Mouse Model. Nucl Med Mol Imaging. 2015;49(3):200-207.
4. Bettio A, et al. Synthesis and preclinical evaluation of a folic acid derivative labeled with 18F for PET imaging of folate receptor-positive tumors. J Nucl Med. 2006;47(7):1153‑1160.
5. Ross TL, et al. Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative. Bioconjug. Chem. 2008;19:2462-2470.
6. Schieferstein H, et al. 18 F-click labeling and preclinical evaluation of a new 18 F-folate for PET imaging. EJNMMI Res. 2013;3:68.
7. Schieferstein H, Ross TL. A polar 18F-labeled amino acid derivative for click labeling of biomolecules. Eur. J. Org. Chem. 2014, 17, 3546-3550.
8. Kettenbach K, et al. A 18F-labeled dibenzocyclooctyne (DBCO) derivative for copper-free click labeling of biomolecules. Med. Chem. Commun. 2016;7:654-657.
9. Kettenbach K, et al. Comparison Study of Two Differently Clicked 18F-Folates-Lipophilicity Plays a Key Role. Pharmaceuticals 2018;11:30.