Studies on some fluorinated polyamines as potential tumor imaging agents [microform]

Two fluorinated polyamine analogues tetrafluoroputrescine (TFP) and N-($\delta$-aminobutyl)-2,2,3,3-tetrafluoro-1,4-diaminobutane (TFP-PUT) were synthesized. A simple reverse-phase liquid chromatographic system with ultraviolet detection at 254 nm was developed for the analysis of TFP. The assay involved pre-column derivatization of TFP with dansyl chloride at pH 6.8-7.5 at 60$\sp\circ$C, followed by separation from putrescine (PUT) and quantitation. The derivatization procedure was adapted for the simultaneous analysis of TFP and PUT. Preliminary data on the protein binding properties of TFP indicated formation of a tight-binding complex rather than binding through a covalent bond. In vitro studies indicated that there was poor uptake of TFP into red blood cells and two breast tumor cell lines, MCF-7 and LY2. Animal studies showed that TFP was found to be rapidly distributed throughout the body of the mice and exhibited first-order pharmacokinetics with a half-life of 70 min.

The tissue distribution of TFP was determined in EMT6 tumor-bearing and/or healthy (control) mice at one hour following a single intraocular bolus dose. The highest level of intact TFP was found in the stomach (up to 21% dose/gram of tissue). However, there was no preferential localization of TFP in the tumor. Fluorine-19 nuclear magnetic resonance (NMR) spectroscopy was used to detect the in vitro uptake of TFP in red blood cells and plasma. It was also used to evaluate the disposition of TFP-PUT in healthy animals following a single iv bolus dose. The animals were sacrificed at 5, 30 and 60 minutes post-administration. Blood levels of TFP-PUT rapidly declined, with no detectable amounts by 60 min. The tissues showed maximal levels of TFP-PUT at 30 minutes with the highest amount localized in the kidneys at this time.