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Updated: Jun 20, 2025
MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent
Published on: September 3, 2013
Evaluation of a bimodal, matched pair theranostic agent targeting prostate-specific membrane antigen
Michael R Lewis1, Alexander W Schaedler2, Khanh-Van Ho3
1Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, United States of America; Molecular Imaging and Theranostics Center, University of Missouri, Columbia, MO, United States of America; Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, United States of America.
Background:
Prostate cancer affects 1 in 6 men, and it is the second‑leading cause of cancer-related death in American men. Surgery is one of the main treatment modalities for prostate cancer, but it often results in incomplete resection margins or complete resection that leads to nerve damage and undesirable side effects. In the present work, we have developed a new bimodal tracer, NODAGA-sCy7.5 PSMAi (prostate-specific membrane antigen inhibitor), labeled with the true matched theranostic pair 64Cu/67Cu and a near-infrared fluorescent dye. This agent could potentially be used for concomitant PET imaging, optical surgical navigation, and targeted radiopharmaceutical therapy.
Methods:
A prostate-specific membrane antigen (PSMA)-targeting urea derivative was conjugated to NODAGA for copper radiolabeling and to the near-infrared fluorophore sulfo-Cy7.5 (sCy7.5). Binding studies were performed in PSMA-positive PC-3 PIP cells, as well as uptake and internalization assays in PC-3 PIP cells and PSMA-negative PC-3 wild type cells. Biodistribution studies of the 64Cu-labeled compound were performed in PC-3 PIP- and PC-3 tumor-bearing mice, and 67Cu biodistributions of the agent were obtained in PC-3 PIP tumor-carrying mice. PET imaging and fluorescence imaging were also performed, using the same molar doses, in the two mouse models.
Results:
The PSMA conjugate bound with high affinity to PSMA-positive prostate cancer cells, as opposed to cells that were PSMA-negative. Uptake and internalization were rapid and PSMA-mediated in PC-3 PIP cells, while only minimal non-specific uptake was observed in PC-3 cells. Biodistribution studies showed specific uptake in PC-3 PIP tumors, while accumulation in PC-3 tumor-bearing mice was low. Furthermore, tumor uptake of the 67Cu-labeled agent in the PC-3 PIP model was statistically equivalent to that of 64Cu. PET and fluorescence imaging at 0.5 nmol per mouse also demonstrated that PC-3 PIP tumors could be clearly detected, while PC-3 tumors showed no tumor accumulation.
Conclusions:
NODAGA-sCy7.5-PSMAi was specific and selective in detecting PSMA-positive, as opposed to PSMA-negative, tumors in mouse models of prostate cancer. This bioconjugate could potentially be used for PET staging with 64Cu, targeted radiopharmaceutical therapy with 67Cu, and/or image-guided surgery with sCy7.5.
Insights
A novel bimodal tracer, NODAGA-sCy7.5 PSMAi, shows high specificity for prostate cancer cells. This agent enables PET imaging, optical navigation, and targeted therapy for improved prostate cancer management.
Area of Science:
- Nuclear medicine and molecular imaging
- Oncology
- Radiopharmaceutical chemistry
Background:
- Prostate cancer is a leading cause of cancer death in men, with surgery often leading to complications.
- Current treatments can result in incomplete resection or nerve damage, highlighting the need for improved diagnostic and therapeutic tools.
- A novel bimodal tracer, NODAGA-sCy7.5 PSMAi, has been developed for prostate cancer.
Purpose of the Study:
- To develop and evaluate a new bimodal tracer, NODAGA-sCy7.5 PSMAi, for prostate cancer.
- To assess its potential for concomitant Positron Emission Tomography (PET) imaging, optical surgical navigation, and targeted radiopharmaceutical therapy.
- To utilize the theranostic pair 64Cu/67Cu and a near-infrared fluorescent dye for dual-modality applications.
Main Methods:
- Conjugation of a prostate-specific membrane antigen (PSMA)-targeting urea derivative to NODAGA and the near-infrared fluorophore sulfo-Cy7.5 (sCy7.5).
- In vitro binding, uptake, and internalization assays using PSMA-positive (PC-3 PIP) and PSMA-negative (PC-3 wild type) cells.
- In vivo biodistribution, PET imaging, and fluorescence imaging studies in mouse models bearing PC-3 PIP or PC-3 tumors using 64Cu and 67Cu.
Main Results:
- The PSMA conjugate demonstrated high affinity and specific, PSMA-mediated uptake and internalization in PSMA-positive PC-3 PIP cells.
- Biodistribution studies showed specific uptake in PC-3 PIP tumors with low accumulation in non-target tissues.
- PET and fluorescence imaging clearly detected PSMA-positive tumors, with 67Cu uptake statistically equivalent to 64Cu.
Conclusions:
- NODAGA-sCy7.5-PSMAi exhibits high specificity and selectivity for PSMA-positive tumors in preclinical prostate cancer models.
- This bioconjugate holds promise for multimodal applications including PET staging (64Cu), targeted radiopharmaceutical therapy (67Cu), and image-guided surgery (sCy7.5).
- The development represents a significant advancement in theranostic agents for prostate cancer management.
