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Development of a New FR-Targeting Agent 99mTc-HYNFA with Improved Imaging Contrast and Comparison of Multimerization and/or PEGylation Strategies for Radio-Folate Modification
- Source :
- Molecular Pharmaceutics; 20240101, Issue: Preprints
- Publication Year :
- 2024
-
Abstract
- This study aims to develop a new folate receptor (FR)-targeting agent for SPECT imaging with improved contrast and evaluate the modification strategies of multimerization and/or PEGylation in the development of new radio-folates. A series of novel folate derivatives have been synthesized and radiolabeled with 99mTc using tricine and TPPTS as coligands. To better investigate their pharmacokinetics, cell uptake, biodistribution, and microSPECT/CT imaging were evaluated. Four radioligands displayed high KB cell uptake after incubation for 2 and 4 h. Presaturated with excess folic acid (FA) resulted in a significant blocking effect in KB cells, indicating specificity of these radioligands toward FR. Biodistribution and microSPECT imaging studies in KB tumor-bearing mice showed that the folate conjugate 99mTc-HYNFA with poly(ethylene glycol) (PEG) and triazole linkage displayed the highest tumor uptake (16.30 ± 2.01 %ID/g at 2 h p.i. and 14.9 ± 0.62 %ID/g at 4 h p.i. in mice biodistribution) and best imaging contrast, indicating promising application prospect. More interestingly, the in vivo performance of this monomeric 99mTc-HYNFA was much better than that of FA multimers and non-PEGylated monomers, suggesting that multimerization may not be a feasible method for the design of radio-folates. PEG linkage rather than FA multimerization should be taken into consideration in the development of folate-based radiopharmaceuticals in the future.
Details
- Language :
- English
- ISSN :
- 15438384 and 15438392
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Molecular Pharmaceutics
- Publication Type :
- Periodical
- Accession number :
- ejs43373489
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.7b00536