Update and Biodistribution of [F-18]FMDHT pET/CT in Normal Healthy Volunteers and Patients With Metastatic Prostate Cancer - A First in Human Subject Study With [F-18] FMDHT
Prostate cancer represents a significant health problem in the United States. This year 179,000 men in the United States will be diagnosed with prostate carcinoma and approximately 25% of them will die of the disease. In addition, the incidence and mortality of prostate carcinoma has been increasing steadily in the United States. Prostate-specific antigen (PSA) levels are commonly used as a biomarker for the detection of prostate cancer. Nonetheless, there is a significant false negative and false positive diagnosis since PSA levels elevate in benign prostatic hyperplasia and prostatitis and decrease in patients taking medications and herbal remedies. Twenty percent of biopsy-proven prostate carcinoma have PSA levels within the normal range, thus confounding the diagnosis based on the PSA screening test. Current diagnostic methods that include transrectal ultrasound (TRUS) and TRUS guided prostate biopsy are logistically difficult and insensitive. These are further complicated by equivocal prostatic biopsy findings such as prostatic intraepithelial neoplasia (PIN) or normal PSA with high clinical suspicion. A tracer with high specificity to prostate cancer related structures at a cellular level would enhance our understanding of the pathophysiology of prostate cancer and would contribute to the detection, localization and quantification of the disease and its metastases. This information will be invaluable in selecting the appropriate treatment regimen.
This study will test the utility of [F-18]FMDHT to image prostate cancer and will evaluate if this radiotracer can differentiate primary prostate cancer in the prostate gland from normal prostate gland itself. More specifically, we will study the distribution kinetics of [F-18]FMDHT in normal healthy humans and in patients with prostate cancer.
As per exploratory IND requirements, we performed toxicity assessment of FMDHT through an outside laboratory (ILS, Inc.) and the results of that study are attached as Appendix A.
Based on our and others data, we hypothesize that:
- [F-18]FMDHT PET/CT will distribute initially in various normal tissues following blood flow pattern and will clear rapidly from tissues with no AR.
- [F-18]FMDHT PET/CT will detect metastatic disease that expresses AR.
- [F-18]FMDHT PET/CT uptake will be elevated in AR-expressing prostate cancer lesions compared to surrounding normal prostate.
In order to progress [F-18]FMDHT into clinic, we are performing a pilot 'first-in-human' biodistribution study in subjects with and without prostate cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Update and Biodistribution of [F-18]FMDHT pET/CT in Normal Healthy Volunteers and Patients With Metastatic Prostate Cancer - A First in Human Subject Study With [F-18] FMDHT|
- To map diffusion and clearance rates of this marker in normal and cancerous tissue. [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]To obtain first-in-man biodistribution data for [F-18]FMDHT with PET/CT imaging in subjects with and without prostate cancer. The results of these tests will be in the form of scans. Distinguishing characteristics will be how quickly the marker clears from the tissues in the scans.
- To determine if [F-18]FMDHT PET/CT uptake in the primary prostate tumor can be differentiated from normal surrounding prostate that will be confirmed with pathologic staining of biopsy or surgical specimens. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
|Study Start Date:||November 2012|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
|Experimental: Healthy Volunteers||Drug: [F-18] fluorinated dihydrotestosterone (FDHT)|
|Experimental: Prostate Cancer Patients||Drug: [F-18] fluorinated dihydrotestosterone (FDHT)|
|United States, North Carolina|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|Principal Investigator:||Pradeep Garg, PhD||Wake Forest School of Medicine|