1 research outputs found
Radiochemistry and In Vivo Imaging of [<sup>45</sup>Ti]Ti-THP-PSMA
Titanium-45 (45Ti) is
a radionuclide with excellent
physical characteristics for use in positron emission tomography (PET)
imaging, including a moderate half-life (3.08 h), decay by positron
emission (85%), and a low mean positron energy of 0.439 MeV. However,
challenges associated with titanium chemistry have led to the underdevelopment
of this radionuclide for incorporation into radiopharmaceuticals.
Expanding on our recent studies, which showed promising results for
the complexation of 45Ti with the tris hydroxypyridinone
(THPMe) chelator, the current work aimed to optimize the
chemistry and imaging attributes of [45Ti]Ti-THP-PSMA as
a new PET radiopharmaceutical. Methods. Radiolabeling
of THP-PSMA was optimized with [45Ti]Ti-citrate at varying
pHs and masses of the precursor. The stability of the radiolabeled
complex was assessed in mouse serum for up to 6 h. The affinity of
[45Ti]Ti-THP-PSMA for prostate-specific membrane antigen
(PSMA) was assessed using LNCaP (PSMA +) and PC3 (PSMA -) cell lines.
In vivo imaging and biodistribution analysis were performed in tumor-bearing
xenograft mouse models to confirm the specificity of the tumor uptake. Results. > 95% of radiolabeling was achieved with a high
specific
activity of 5.6 MBq/nmol under mild conditions. In vitro cell binding
studies showed significant binding of the radiolabeled complex with
the PSMA-expressing LNCaP cell line (11.9 ± 1.5%/mg protein-bound
activity) compared to that with the nonexpressing PC3 cells (1.9 ±
0.4%/mg protein-bound activity). In vivo imaging and biodistribution
studies confirmed specific uptake in LNCaP tumors (1.6 ± 0.27%
ID/g) compared to that in PC3 tumors (0.39 ± 0.2% ID/g). Conclusion. This study showed a simple one-step radiolabeling
method for 45Ti with THP-PSMA under mild conditions (pH
8 and 37 °C). In vitro cell studies showed promise, but in vivo
tumor xenograft studies indicated low tumor uptake. Overall, this
study shows the need for more chelators for 45Ti for the
development of a PET radiopharmaceutical for cancer imaging