The long-term goal of this project is to develop a theranostic (for both diagnosis and therapy) agent targetingneurotensin receptor 1 (NTSR1) for prostate cancer management.Prostate cancer is the second-leading cause of cancer deaths for men in the United States. Approximately 1 in 9 men will be diagnosed with prostate cancer in their lifetime. Despite recent developments in its diagnosis andtreatments, the advanced stages of prostate cancer still have poor survival rates. In fact, patients with advancedstage prostate cancer may initially respond to hormone therapy with more than 90% rate, but they could relapseinto the hormone-refractory state and generally die within 3 years. Clearly, this urgent unmet need warrantsfurther exploration of clinically relevant molecular targets for patient screening, detection of metastatic disease,and corresponding treatment strategies. Accumulating evidence suggests that neurotensin (NTS) andneurotensin receptors (NTSRs) play key roles in prostate cancer progression. In our recent histology analysis,all examined PSMA-negative prostate cancer tissues were found to have positive NTSR1 expression, suggestingthe potential complementary role of NTSR1 targeted imaging/therapy towards PSMA based imaging/therapy. Inanother word, NTSR1 targeted therapy could be used when PSMA targeted therapy fails.In this project, AccuNovo Biotech Inc. will partner with Profs. Zibo Li and Rihe Liu at UNC Chapel Hill to developnew theranostic agents targeting NTSR1 based on the recent progress on ligand discovery. Recently, we foundthat the introduction of crosslinked polyamines into SR142948A (leading to new agent SR-CP-05) could increasethe tumor uptake by 10 times compared with peptide-based agent. This discovery offered us an unprecedentedopportunity to develop NTSR1 targeted theranostic agents. We will focus on imaging agent development inPhase I. The specific aims of this proposal are: Aim 1: Develop 64Cu labeled NTSR1-targeting PET agents withhigh and persistent tumor uptake; Aim 2: Perform side-by-side comparison of lead agents in prostate cancermouse models and select the best agent for Phase II efficacy study. The success of this project will not only leadto an accurate imaging-based method to efficiently detect NTSR1 expression in prostate cancer (for patientscreening and treatment monitoring), but also be further developed into a radionuclide-based agent for prostatecancer therapy.
Public Health Relevance Statement: Project Narrative
There is an urgent and unmet clinical need to develop new imaging and therapeutic methods for the management
of prostate cancer patient. Based on the SR-CP-05 ligand and new chelators, novel radiolabeled agents will be
prepared for NTSR1 targeted imaging and therapy applications. These novel agents may be used for patient
screening, treatment monitoring, and targeted radionuclide-based therapy, all of which are anticipated to impact
the care of patients with prostate cancer.
Project Terms:
