First-in-Human Phase 0 Study of AB001, a Prostate-Specific Membrane Antigen-Targeted ²¹²Pb Radioligand, in Patients...

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge.
• Prostate-specific membrane antigen (PSMA)-targeted therapies offer a promising approach for mCRPC treatment.
• Alpha-emitters like ²¹²Pb hold potential for targeted radionuclide therapy due to their high linear energy transfer.

Purpose of the Study:

• To investigate the feasibility of gamma-camera imaging for assessing the biodistribution and metastatic lesion uptake of AB001, a ²¹²Pb-labeled PSMA-targeted small molecule.
• To evaluate the safety and tolerability of a microdose of AB001 in patients with mCRPC.
• To explore the in vivo stability and pharmacokinetic profile of AB001.

Main Methods:

• A phase 0 clinical trial involving three patients with progressive mCRPC.
• Administration of a microdose of ²¹²Pb-labeled AB001 (9.4 ± 0.3 MBq).
• Assessment of biodistribution using planar gamma-camera and SPECT/CT imaging at 1-3 h and 16-24 h post-administration, along with whole-body probe measurements and blood analysis for stability and clearance.

Main Results:

• AB001 was safely administered, with no reported complications or adverse reactions.
• Gamma-camera imaging visualized AB001 uptake in one PSMA-expressing metastatic lesion.
• Biodistribution showed expected uptake in kidneys, liver, and urinary bladder, with an effective half-life of 8 hours; AB001 demonstrated in vivo stability.

Conclusions:

• The ²¹²Pb-based radioligand AB001 is safe for administration in mCRPC patients.
• Gamma-camera imaging of AB001 is feasible, even at microdoses, and can demonstrate metastatic targeting.
• The promising biodistribution and clearance profile of AB001 warrant further clinical investigation for mCRPC.