Impact of ¹⁸F-PSMA-1007 Uptake in Prostate Cancer Using Different Peptide Concentrations: Preclinical PET/CT Study on...

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology Imaging

Background:

• Low molar activity (MA) of PET radioligands can lead to underestimation of target quantity due to unlabeled ligand competition.
• Prostate-specific membrane antigen (PSMA) is a key target for prostate cancer imaging and therapy.
• ¹⁸F-PSMA-1007 is a PET radioligand used for PSMA-targeted imaging.

Purpose of the Study:

• To evaluate how varying peptide concentrations (affecting MA) of ¹⁸F-PSMA-1007 impact its whole-body distribution.
• To assess the effect of MA on ¹⁸F-PSMA-1007 uptake in PSMA-positive tumors and normal organs.
• To determine if optimizing MA can mitigate off-target effects, particularly in salivary glands.

Main Methods:

• Mouse xenograft models (LNCaP, PSMA-positive prostate cancer) were used (n=18).
• Mice were divided into high, medium, and low MA groups of ¹⁸F-PSMA-1007.
• Static PET scans were performed 1 hour post-injection; SUV_mean in tumors and organs was analyzed. Immunohistochemistry and Western blot confirmed PSMA expression.

Main Results:

• Lower MA (low-MA group) significantly decreased ¹⁸F-PSMA-1007 tumor uptake compared to high-MA and medium-MA groups.
• Salivary gland uptake was significantly lower in low-MA and medium-MA groups compared to the high-MA group.
• The tumor-to-salivary gland SUV_mean ratio increased with decreasing MA, indicating improved target-to-background contrast.

Conclusions:

• Decreasing the MA of ¹⁸F-PSMA-1007 reduces uptake in both tumors and, more significantly, in normal salivary glands.
• Optimizing the MA level of ¹⁸F-PSMA-1007 offers a potential strategy to minimize adverse effects in salivary glands during PSMA-targeted therapy.
• PSMA expression was confirmed in tumors, with low expression in salivary glands and kidneys, correlating with observed radiotracer distribution.