Radiopharmaceutical Design and Molecular Imaging

 

How to cite: Ferrara KW. Radiopharmaceutical Design and Molecular Imaging. Grand Rounds in Urology. September 15, 2025. Accessed Oct 2026. https://grandroundsinurology.com/radiopharmaceutical-design-and-molecular-imaging/

Summary

Katherine Whittaker Ferrara, PhD, Division Chief   of the Molecular Imaging Program and Professor of Radiology, Stanford University, Stanford, California, highlights translational research that integrates radiopharmaceutical design, molecular imaging, and transcriptomics in prostate cancer. She notes that the program spans Stanford, UCLA, and Tufts, and includes simplified radiolabeling, biomarker analysis, molecular dynamics, and peptide design for imaging and therapy.

Dr. Ferrara reports findings from preliminary retrospective analyses in patients imaged with Gallium-68 RM2 prior to prostatectomy. Using spatial transcriptomics, her group correlated imaging signals with histology. Early results indicated that Gallium-68 RM2 detected lesions confirmed by pathology. Transcriptomic sequencing at thousands of locations per patient allowed mapping of prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) expression.

Findings suggested that prostate-specific membrane antigen (PSMA) expression levels were generally higher than those of gastrin-releasing peptide receptor (GRPR), but with a similar spatial distribution. These patterns agreed with prior single-cell analyses, which showed that GRPR had a narrower dynamic range. Integrative clustering identified a cancer-like phenotype with increased GRPR and PSMA expression. Transcriptomic correlation analyses also implicated TMEM45B as a relevant marker alongside PSMA and GRPR.

Pseudotime analysis revealed increasing PSMA expression with progression from pre-cancerous to invasive states, with GRPR showing more limited increases. The work led to the identification of five target proteins, with new peptides in development to achieve high nanomolar affinities. Dr. Ferrara emphasizes the translational goal of advancing peptide-based probes and radiopharmaceuticals for precision imaging and therapy.

The Global Summit on Precision Diagnosis and Treatment of Prostate Cancer is a unique multi-disciplinary forum organized to inform the key health care stakeholders about the emerging advances in clinical case and research and create a consensus-based vision for the future of precision care and educational and research strategy for its realization. The mission of the Summit is to fill the currently existing gap between the key experts of in vivo imaging, the world authorities in the in vitro fluid- and tissue-based molecular diagnostics, including genomics, and thought leaders in the development of novel observation strategies (e.g., active surveillance, or AS) and therapeutic interventions.