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Radiochemistry and In Vivo Imaging of [ 45 Ti]Ti-THP-PSMA.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2024 Feb 05; Vol. 21 (2), pp. 822-830. Date of Electronic Publication: 2024 Jan 03. - Publication Year :
- 2024
-
Abstract
- Titanium-45 ( <superscript>45</superscript> Ti) 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 <superscript>45</superscript> Ti with the tris hydroxypyridinone (THP <superscript>Me</superscript> ) chelator, the current work aimed to optimize the chemistry and imaging attributes of [ <superscript>45</superscript> Ti]Ti-THP-PSMA as a new PET radiopharmaceutical. Methods . Radiolabeling of THP-PSMA was optimized with [ <superscript>45</superscript> Ti]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 [ <superscript>45</superscript> Ti]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 <superscript>45</superscript> Ti 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 <superscript>45</superscript> Ti for the development of a PET radiopharmaceutical for cancer imaging.
- Subjects :
- Male
Humans
Animals
Mice
Radiopharmaceuticals
Radiochemistry
Tissue Distribution
Titanium
Glutamate Carboxypeptidase II metabolism
Antigens, Surface metabolism
Positron-Emission Tomography
Radioisotopes
Chelating Agents
Cell Line, Tumor
Positron Emission Tomography Computed Tomography methods
Prostatic Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 38173242
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.3c00917