1. Synthesis of a new HYNIC-DAPI derivative for labelling with ⁹⁹ᵐTechnetium and its in vitro evaluation in an FRTL5 cell line
- Author
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Ferl, Sandra, Wunderlich, Gerd, Smits, René, Hoepping, Alexander, Naumann, Anne, and Kotzerke, Jörg
- Subjects
Fluorochrom, Fluoreszenzfarbstoff, Biokonjugation, DNA-bindende Einheiten, Zellkompartimente ,Fluorochrom, fluorescent dye, bioconjugation, DNA-binding moieties, cell compartments ,ddc:540 - Abstract
4′,6-Diamidine-2-phenylindole (DAPI) is a common fluorochrome that is able to bind to deoxyribonucleic acid (DNA) with distinct, sequence-dependent enhancement of fluorescence. This work presents the synthesis of a new multifunctional compound that includes the fluorescent dye as a ⁹⁹ᵐTechnetium (⁹⁹ᵐTc) carrier. A new technique for the bioconjugation of DAPI with 6-hydrazinonicotinic acid (HYNIC) through an amide linkage was developed. The radiolabelling was performed with HYNIC as a chelator and N-IJ2-hydroxy-1,1-bisIJhydroxymethyl)ethyl)glycine (tricine) as a coligand. Furthermore, experimental evidence showed that ⁹⁹ᵐTc complexes with DAPI as DNA-binding moieties are detectable in living Fischer rat thyroid follicular cell line 5 (FRTL5) and their nuclei. The investigations indicated further that the new HYNIC-DAPI derivative is able to interact with double-stranded DNA. This establishes the possibility of locating ⁹⁹ᵐTc in close proximity to biological structures of living cells, of which especially the genetic information-carrying cell compartments are at the centre of interest. In this context, further investigations are related to the radiotoxic effects of DNA-bound ⁹⁹ᵐTc-HYNIC-DAPI derivatives and dosimetric calculations.
- Published
- 2015