45Ti targeted tracers for PET imaging of PSMA

PURPOSE: Positron Emission Tomography is an important molecular imaging technique for detection and diagnoses of various disease states. This work aims to develop novel titanium-45 (t_½ = 3.08 h) PET tracers using Prostate Specific Membrane Antigen (PSMA) targeting vectors for imaging of prostate cancer as proof of concept for this relatively unexplored isotope. PROCEDURES: Titanium-45 was produced on the University of Alabama at Birmingham (UAB) TR24 cyclotron using proton bombardments on natural scandium foils and separated using procedures described previously [1]. After purification, Titanium-45 was used to radiolabel two PSMA-targeting molecules; DFO-DUPA and LDFC-DUPA. Radiochemical yields were determined via radio-high purity liquid chromatography (radioHPLC). The radiolabeled compounds were tested both in vitro and in vivo using PSMA+ cell lines (LNCaP and 22Rv1) and PSMA- cell lines (PC3). RESULTS: Titanium-45 was produced and purified in yields suitable for research studies. Radiochemical yields of up to 98 ± 1% were achieved with DFO-DUPA and 92 ± 7% with LDFC-DUPA. PSMA specific targeting was observed in vitro in PSMA positive cells (LNCaP (0.6% ± 0.05%) and confirmed by blocking (0.15% ± 0.04%) (P < 0.0001)), compared to uptake in the PSMA negative cells (PC3 (0.07% ± 0.008%)) and confirmed by blocking (0.07% ± 0.01%) (P = 0.5253). In vivo studies demonstrated statistically significant uptake in LNCaP tumors (2.3% ± 0.3% ID/g) compared to PC3 tumor uptake (0.1% ± 0.07%). CONCLUSIONS: This work shows that titanium-45 can be used to radiolabel PSMA targeting compounds with high radiochemical yields. These radiolabeled compounds remain intact in serum for at least two half-lives of titanium-45, showing that these compounds would be appropriate for implementation in the clinical setting. This study shows the feasibility of using titanium-45 as positron emitting radiometal for use in imaging PSMA+ prostate cancer, and illustrates that further research is in this area is warranted.