Preclinical Evaluation of [²¹²Pb]Pb-ADVC001: A Prostate-Specific Membrane Antigen-Targeted α-Therapy for Prostate...

Area of Science:

• Oncology
• Radiopharmaceutical Therapy
• Nuclear Medicine

Background:

• Prostate-specific membrane antigen (PSMA)-targeted therapies are advancing treatment for metastatic castration-resistant prostate cancer.
• Targeted alpha therapy offers a potent approach for cancer treatment due to high energy deposition over short ranges.

Purpose of the Study:

• To characterize a novel PSMA-targeted alpha therapy agent, ADVC001, utilizing Lead-212 (²¹²Pb).
• To evaluate the in vitro and in vivo efficacy and safety of ²¹²Pb-ADVC001 in preclinical prostate cancer models.

Main Methods:

• Binding affinity of ADVC001 to PSMA was assessed using enzymatic and radioligand binding assays.
• In vitro cytotoxicity was evaluated in prostate cancer cell lines with varying PSMA expression levels.
• In vivo pharmacokinetics, biodistribution, and efficacy were studied in PSMA-positive xenograft models.

Main Results:

• ADVC001 demonstrated high binding affinity to PSMA and specific cytotoxic activity against PSMA-expressing cells.
• ²¹²Pb-ADVC001 showed favorable biodistribution with rapid tumor uptake and clearance from normal tissues.
• Significant survival improvements were observed in preclinical models treated with ²¹²Pb-ADVC001 compared to controls and ¹⁷⁷Lu-PSMA-I&T.

Conclusions:

• ²¹²Pb-ADVC001 exhibits potent and specific anti-cancer activity in preclinical models.
• The favorable safety and efficacy profile supports the further clinical development of ²¹²Pb-ADVC001 for prostate cancer treatment.