FDG and DHT PET Imaging for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: Any Age
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Disqualifiers: Anaphylactic reaction, Hepatic issues, Renal issues
No Placebo Group
Trial Summary
What is the purpose of this trial?This study will use PET scans, which is a type of x-ray test that uses a radiotracer, to see whether these scans may be better able to find places in the body where your prostate cancer may have spread.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications.
What data supports the effectiveness of the drug used in the FDG and DHT PET Imaging for Prostate Cancer trial?
Research shows that [18F]FDHT PET imaging can effectively target androgen receptors in prostate cancer, helping to assess the cancer's response to therapy. This imaging method is promising for predicting how well patients might respond to hormone-based treatments.
12345Is FDG and DHT PET Imaging for Prostate Cancer safe for humans?
Research shows that [18F]FDHT, used in PET imaging for prostate cancer, has been evaluated for safety in humans. The main concern is the radiation dose to the urinary bladder, but overall, it is considered safe with careful monitoring of radiation exposure.
24678How does the drug FDHT differ from other prostate cancer treatments?
FDHT is unique because it uses PET imaging to directly target and visualize androgen receptors in prostate cancer, helping to assess the cancer's response to treatment. This approach is different from standard treatments as it provides a non-invasive way to monitor the effectiveness of therapies by measuring changes in androgen receptor levels.
12346Eligibility Criteria
Men with confirmed prostate cancer showing progression through new bone lesions, increased soft tissue disease, or rising PSA levels. They must have visible cancer signs on CT, MRI, or bone imaging and functionally adequate kidneys and liver. Those with severe kidney issues, past severe reactions to the PET scan tracers, or significant liver dysfunction cannot join.Inclusion Criteria
Patients with histologically confirmed prostate cancer.
Progressive disease manifest by either: Imaging modalities: Bone Imaging: New osseous lesions on bone imaging (bone scintigraphy or NaF PET scan) and/or MRI or CT: An increase in measurable soft tissue disease, or the appearance of new sites of disease. Or Biochemical progression: A minimum of three rising PSA values from a baseline that are obtained 1 week or more apart, or 2 measurements 2 or more weeks apart.
Informed consent.
+1 more
Exclusion Criteria
Renal: Creatinine >1.5 x ULN or creatinine clearance < 60 mL/min
Previous anaphylactic reaction to either FDHT or FDG
Hepatic: Bilirubin > 1.5 x upper limit of normal (ULN), AST/ALT >2.5 x ULN, albumin < 2 g/dl, and GGT > 2.5 x ULN IF Alkaline phosphatase > 2.5 x ULN
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging Evaluation
Participants undergo PET scans using FDG and FDHT to evaluate cancer spread and metabolism
4-8 weeks
Multiple imaging visits
Follow-up
Participants are monitored for changes in FDG and FDHT uptake and correlation with PSA levels
2 years
Participant Groups
The trial is testing two PET scan radiotracers: [18F]-Fluoro-2-Deoxy-D-Glucose (FDG) and [18F] Dihydro-Testosterone (FDHT), to see if they can more accurately detect where prostate cancer has spread in the body compared to current methods.
1Treatment groups
Experimental Treatment
Group I: 1Experimental Treatment1 Intervention
\[18F\]-Fluoro-2-Deoxy-D-Glucose and -\[18F\] Dihydro-Testosterone
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Westchester (Consent only)Harrison, NY
Memorial Sloan Kettering Commack (Consent only)Commack, NY
Memorial Sloan Kettering Cancer CenterNew York, NY
Memorial Sloan Kettering Nassau (Consent Only)Uniondale, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Pharmacokinetic assessment of the uptake of 16beta-18F-fluoro-5alpha-dihydrotestosterone (FDHT) in prostate tumors as measured by PET. [2021]The aim of this study was to develop a clinically applicable noninvasive method to quantify changes in androgen receptor (AR) levels based on (18)F-16beta-fluoro-5alpha-dihydrotestosterone ((18)F-FDHT) PET in prostate cancer patients undergoing therapy.
Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. [2022]This trial was an initial assessment of the feasibility, in vivo targeting, and biokinetics of 16beta-(18)F-fluoro-5alpha-dihydrotestosterone ((18)F-FDHT) PET in patients with metastatic prostate cancer to assess androgen receptor expression.
Sensitivity of 18F-fluorodihydrotestosterone PET-CT to count statistics and reconstruction protocol in metastatic castration-resistant prostate cancer. [2020]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Whole body [18F]-fluorodihydrotestosterone positron emission tomography ([18F]FDHT PET) imaging directly targets the androgen receptor and is a promising prognostic and predictive biomarker in metastatic castration-resistant cancer (mCRPC). To optimize [18F]FDHT PET-CT for diagnostic and response assessment purposes, we assessed how count statistics and reconstruction protocol affect its accuracy, repeatability, and lesion detectability.
PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. [2022]16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) is a promising new PET radiopharmaceutical for the imaging of prostate cancer. A recent clinical trial provided the opportunity for refinement of normal-tissue radiation-absorbed dose estimates based on quantitative PET. The objective of the current study was to derive estimates of normal-tissue absorbed doses for (18)F-FDHT administered to patients with advanced prostate cancer.
Androgen Receptor Imaging in the Management of Hormone-Dependent Cancers with Emphasis on Prostate Cancer. [2023]Prostate cancer is dependent on the action of steroid hormones on the receptors. Endocrine therapy inhibits hormone production or blocks the receptors, thus providing clinical benefit to many, but not all, oncological patients. It is difficult to predict which patient will benefit from endocrine therapy and which will not. Positron Emission Tomography (PET) imaging of androgen receptors (AR) may provide functional information on the likelihood of endocrine therapy response in individual patients. In this article, we review the utility of [18F]FDHT-PET imaging in prostate, breast, and other hormone-dependent cancers expressing AR. The methodologies, development, and new possibilities are discussed as well.
Positron tomographic assessment of androgen receptors in prostatic carcinoma. [2018]The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer.
Report on the PET/CT Image-Based Radiation Dosimetry of [18F]FDHT in Women, a Validated Imaging Agent with New Applications for Evaluation of Androgen Receptor Status in Women with Metastatic Breast Cancer. [2023]In a prospective clinical trial, [18F]fluoro-5α-dihydrotestosterone ([18F]FDHT), the radiolabeled analog of the androgen dihydrotestosterone, was used as a PET/CT imaging agent for in vivo assessment of metastatic androgen receptor-positive breast cancer in postmenopausal women. To our knowledge, this article presents the first report of PET/CT image-based radiation dosimetry of [18F]FDHT in women. Methods: [18F]FDHT PET/CT imaging was performed on a cohort of 11 women at baseline before the start of therapy and at 2 additional time points during selective androgen receptor modulator (SARM) therapy for androgen receptor-positive breast cancer. Volumes of interest (VOIs) were placed over the whole body and within source organs seen on the PET/CT images, and the time-integrated activity coefficients of [18F]FDHT were derived. The time-integrated activity coefficients for the urinary bladder were calculated using the dynamic urinary bladder model in OLINDA/EXM software, with biologic half-life for urinary excretion derived from VOI measurements of the whole body in postvoid PET/CT images. The time-integrated activity coefficients for all other organs were calculated from VOI measurements in the organs and the physical half-life of 18F. Organ dose and effective dose calculations were then performed using MIRDcalc, version 1.1. Results: At baseline before SARM therapy, the effective dose for [18F]FDHT in women was calculated as 0.020 ± 0.0005 mSv/MBq, and the urinary bladder was the organ at risk, with an average absorbed dose of 0.074 ± 0.011 mGy/MBq. Statistically significant decreases in liver SUV or uptake of [18F]FDHT were found at the 2 additional time points on SARM therapy (linear mixed model, P < 0.05). Likewise, absorbed dose to the liver also decreased by a small but statistically significant amount at the 2 additional time points (linear mixed model, P < 0.05). Neighboring abdominal organs of the gallbladder wall, stomach, pancreas, and adrenals also showed statistically significant decreases in absorbed dose (linear mixed model, P < 0.05). The urinary bladder wall remained the organ at risk at all time points. Absorbed dose to the urinary bladder wall did not show statistically significant changes from baseline at any of the time points (linear mixed model, P ≥ 0.05). Effective dose also did not show statistically significant changes from baseline (linear mixed model, P ≥ 0.05). Conclusion: Effective dose for [18F]FDHT in women before SARM therapy was calculated as 0.020 ± 0.0005 mSv/MBq. The urinary bladder wall was the organ at risk, with an absorbed dose of 0.074 ± 0.011 mGy/MBq.
Synthesis of 11 beta-[18F]fluoro-5 alpha-dihydrotestosterone and 11 beta-[18F]fluoro-19-nor-5 alpha-dihydrotestosterone: preparation via halofluorination-reduction, receptor binding, and tissue distribution. [2019]We have prepared 11 beta-fluoro-5 alpha-dihydrotestosterone (11 beta-F-DHT, 1) and 11 beta-fluoro-19-nor-5 alpha-dihydrotestosterone (11 beta-F-19-nor-DHT, 2) in order to investigate the properties of these new androgens labeled with fluorine-18 as potential androgen receptor (AR)-based imaging agents for prostate cancer. These compounds were synthesized in 6 steps from hydrocortisone and in 13 steps from 1,4-androstadiene-3,11,17-trione, respectively. Relative binding affinities (RBA) of 11 beta-F-DHT and 11 beta-F-19-nor-DHT to AR are 53.1 and 75.3 (R1881 = 100), respectively, the latter being the highest reported among fluorine-substituted androgens. The fluorination step, which involves addition of halogen fluoride across the 9(11)-double bond, followed by reductive dehalogenation at the 9 alpha-position has been adapted to introduce a fluorine-18-label at the 11 beta-position of DHT and 19-nor-DHT. The two high-affinity F-18-labeled ligands [18F]-1 and [18F]-2 were evaluated in vivo, in tissue distribution studies using diethylstilbestrol-pretreated mature male rats. 11 beta-F-DHT shows high prostate uptake and selective prostate to blood and prostate to muscle uptake ratios, the latter two ratios increasing from 5 and 8 at 1 h to 12 and 19 at 4 h postinjection. Moreover, this compound has low uptake in bone, displaying the lowest in vivo defluorination among all androgens labeled with fluorine-18 tested so far. The in vivo properties of 11 beta-F-DHT in rats are thus favorable for imaging of prostate cancer. On the other hand, 11 beta-F-19-nor-DHT shows low prostate uptake with low selectivity and high uptake in liver, kidney, and bladder. Even though this ligand has the highest RBA and undergoes little metabolic defluorination, it appears to suffer from rapid metabolism in vivo. Therefore, it is apparent that the biodistribution properties of androgens are affected by their structure and metabolism as well as by their RBA.