⁶⁴Cu-DOTHA₂-PSMA, a Novel PSMA PET Radiotracer for Prostate Cancer with a Long Imaging Time Window

• Main Authors: Marie-Christine Milot (Author), Ophélie Bélissant Benesty (Author), Véronique Dumulon-Perreault (Author), Samia Ait-Mohand (Author), Patrick O. Richard (Author), Étienne Rousseau (Author), Brigitte Guérin (Author)
• Format: Book
• Published: MDPI AG, 2022-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Prostate cancer imaging and late-stage management can be improved with prostate-specific membrane antigen (PSMA)-targeting radiotracers. We developed a PSMA positron emission tomography (PET) radiotracer, DOTHA₂-PSMA radiolabeled with ⁶⁴Cu (T_1/2: 12.7 h), to leverage its large imaging time window. This preclinical study aimed to evaluate the biological and imaging properties of ⁶⁴Cu-DOTHA₂-PSMA. Its stability was assessed in plasma ex vivo and in mice. Cellular behavior was studied for up to 48 h in LNCaP cells. Biodistribution studies were performed in balb/c mice for up to 48 h. Dynamic (1 h) and static (4 h and 24 h) PET imaging was completed in LNCaP tumor-bearing mice. ⁶⁴Cu-DOTHA₂-PSMA was stable ex vivo in plasma and reached cellular internalization up to 34.1 ± 4.9% injected activity (IA)/10⁶ cells at 48 h post-injection (p.i.). Biodistribution results showed significantly lower uptake in kidneys than ⁶⁸Ga-PSMA-617, our reference PET tracer (<i>p</i> < 0.001), but higher liver uptake at 2 h p.i. (<i>p</i> < 0.001). PET images showed ⁶⁴Cu-DOTHA₂-PSMA's highest tumoral uptake at 4 h p.i., with a significant difference between blocked and non-blocked groups from the time of injection to 24 h p.i. The high stability and tumor uptake with a long tumor imaging time window of ⁶⁴Cu-DOTHA₂-PSMA potentially contribute to the prostate cancer theranostic approach and its local recurrence detection.

Item Description

10.3390/ph15080996
1424-8247