Translational and First-in-Human Positron Emission Tomography Targeting Prostatic Acid Phosphatase in Prostate Cancer...

Area of Science:

• Oncology
• Nuclear Medicine
• Radiochemistry

Background:

• Prostate-specific membrane antigen (PSMA)-targeted agents are vital for prostate cancer (PC) management but face limitations due to variable PSMA expression and off-target uptake.
• Prostatic acid phosphatase (ACP3) presents a novel, highly specific target for PC theranostics.

Purpose of the Study:

• To evaluate the first-in-human positron emission tomography (PET) imaging performance of [⁶⁸Ga]Ga-OncoACP3-DOTA, a novel ACP3-targeted radioligand.
• To compare the diagnostic utility of [⁶⁸Ga]Ga-OncoACP3-DOTA with the established [¹⁸F]PSMA-1007 tracer in patients with PC.

Main Methods:

• A cohort of 25 PC patients underwent matched PET scans using both [⁶⁸Ga]Ga-OncoACP3-DOTA and [¹⁸F]PSMA-1007.
• Biodistribution, tumor uptake, and lesion detection were compared between the two tracers.
• Statistical analysis, including the Wilcoxon rank-sum test, was employed to assess differences in performance.

Main Results:

• [⁶⁸Ga]Ga-OncoACP3-DOTA demonstrated significantly lower background uptake in salivary glands and kidneys compared to [¹⁸F]PSMA-1007 (p < 0.002).
• No significant differences in maximum standardized uptake value (SUV_max) were observed between the tracers for localized or metastatic PC.
• Improved performance favoring [⁶⁸Ga]Ga-OncoACP3-DOTA was noted in 11 of 25 matched scans, while [¹⁸F]PSMA-1007 showed better performance in 8 of 25.

Conclusions:

• [⁶⁸Ga]Ga-OncoACP3-DOTA exhibits favorable biodistribution with intense tumor uptake and low off-target activity, supporting its potential in PC theranostics.
• The ACP3-targeted tracer warrants further investigation in clinical trials for PET imaging and radioligand therapy.
• This novel agent may offer a valuable alternative or complementary tool to PSMA-targeted approaches in managing prostate cancer.