Radiolabeling of Quinazoline Derivatives

All solvents and laboratory chemicals were reagent grade and were used without further purification. The HPLC-grade solvents for high-performance liquid chromatography (HPLC) were degassed by a helium flux before and during use. IR spectra were recorded using the Brucker™ Alpha II™ FT-IR/ATR Spectrometer between 4000–400 cm⁻¹. NMR spectra were recorded on a Bruker 250 MHz or 500 MHz Avance DRX spectrometer using the residual solvent peak as a reference. HPLC analysis was performed on a Waters 600 chromatography system coupled to a Waters 2487 Dual l Absorbance detector and a Gabi gamma detector from Raytest. Separations were achieved on a Nucleosil C18 (10 mm, 250 mm × 4 mm) column eluted with a binary gradient system at a 1 mL/min flow rate. Mobile phase A was methanol containing 0.1% trifluoroacetic acid, while mobile phase B was water containing 0.1% trifluoroacetic acid. The elution gradient was 0–1 min 95% B (5% A), followed by a linear gradient to 85% A (15% B) in 8 min. This composition was held for 17 min. After a column wash with 95% A for 10 min, the column was re-equilibrated by applying the initial conditions (95% B) for 10 min prior to the next injection.
[^99mTc]NaTcO₄ was obtained in physiological saline as a commercial ⁹⁹Mo/^99mTc generator eluate (Ultra-Technekow™ V4 Generator, Curium Pharma, Petten, Netherlands). 6-Amino-4-[(3-bromophenyl)amino] quinazoline (1) [21 (link),22 (link)], N-(2-pyridylmethyl)aminoethyl acetate (PAMA) (3) [23 (link)] and the rhenium precursors ReBr(CO)₅ and fac-[Net₄]₂[ReBr₃(CO)₃] [24 (link)] as well as the radioactive precursor fac-[^99mTc][Tc(OH₂)₃(CO)₃]⁺ [25 (link)] have been synthesized according to the literature methods.