FDG and DHT PET Imaging for Prostate Cancer

Recruiting at 6 trial locations

Overseen By Michael Morris, M.D., PH.D.

Age: Any Age

Sex: Male

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Anaphylactic reaction, Hepatic issues, Renal issues

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

300 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{2 4 6 7 8}

How 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. ^{1 2 3 4 6}

Research Team

Michael Morris, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility 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.

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

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

Treatment Details

Interventions

• -[18F] Dihydro-Testosterone
• [18F]-Fluoro-2-Deoxy-D-Glucose

Trial Overview 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.

Participant Groups

Group I: 1 Experimental Treatment 1 Intervention

\[18F\]-Fluoro-2-Deoxy-D-Glucose and -\[18F\] Dihydro-Testosterone

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

This study developed a noninvasive method using (18)F-FDHT PET to quantify androgen receptor (AR) levels in prostate cancer patients, involving 38 patients in total, which could help in assessing treatment response.

The research found that the uptake of (18)F-FDHT in prostate cancer lesions stabilizes within 20 minutes, and the best pharmacokinetic model indicated that the net uptake parameter could serve as a surrogate measure for AR expression, potentially aiding in the management of metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic assessment of the uptake of 16beta-18F-fluoro-5alpha-dihydrotestosterone (FDHT) in prostate tumors as measured by PET. Beattie, BJ., Smith-Jones, PM., Jhanwar, YS., et al.[2021]

The study involved 7 patients with metastatic prostate cancer and assessed the feasibility of using (18)F-FDHT PET scans to evaluate androgen receptor expression, showing that (18)F-FDHT effectively localizes to tumor sites.

(18)F-FDHT PET detected 78% of lesions identified by conventional imaging, indicating its potential as a valuable tool for analyzing androgen receptors in prostate cancer, although testosterone treatment reduced its uptake in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. Larson, SM., Morris, M., Gunther, I., et al.[2022]

In a study involving 14 patients with metastatic castration-resistant prostate cancer (mCRPC), reducing the acquisition time for [18F]FDHT PET scans from 3 minutes to 1.5 minutes per bed position maintained an acceptable repeatability for SUVpeak measurements, which is important for monitoring treatment response.

The novel EARL2 reconstruction method showed higher variability in SUVmax measurements compared to the EARL1 method, indicating that while lesion detectability was minimally affected by reduced acquisition time, the choice of reconstruction protocol can significantly impact the accuracy of SUV measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity of 18F-fluorodihydrotestosterone PET-CT to count statistics and reconstruction protocol in metastatic castration-resistant prostate cancer. Cysouw, MCF., Kramer, GM., Heijtel, D., et al.[2020]

The study estimated the normal-tissue radiation-absorbed doses for the PET radiopharmaceutical 16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) in 7 prostate cancer patients, finding that the maximum absorbed dose to the urinary bladder wall was 0.0151 cGy/MBq.

To keep the absorbed dose below the recommended maximum of 5 cGy per administration, a maximum dose of 331 MBq of FDHT is suggested, ensuring patient safety during imaging procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. Zanzonico, PB., Finn, R., Pentlow, KS., et al.[2022]

Endocrine therapy for prostate cancer can be effective by inhibiting hormone production or blocking hormone receptors, but predicting which patients will benefit remains challenging.

[18F]FDHT-PET imaging of androgen receptors may help identify patients who are more likely to respond to endocrine therapy, potentially improving treatment outcomes in hormone-dependent cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen Receptor Imaging in the Management of Hormone-Dependent Cancers with Emphasis on Prostate Cancer. Kairemo, K., Hodolic, M.[2023]

The study demonstrated that FDHT-PET imaging is feasible for detecting prostate cancer, with a sensitivity of 63% and the ability to identify 86% of known lesions, as well as 17 unsuspected lesions in some patients.

The decrease in FDHT uptake after administering the AR antagonist flutamide indicates that the binding of FDHT to tumors is receptor-mediated, suggesting its potential as a targeted imaging agent for assessing androgen receptor activity in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron tomographic assessment of androgen receptors in prostatic carcinoma. Dehdashti, F., Picus, J., Michalski, JM., et al.[2018]

In a clinical trial involving 11 postmenopausal women, the effective dose of the PET imaging agent [18F]FDHT was determined to be 0.020 mSv/MBq, indicating a low radiation exposure for patients.

The urinary bladder was identified as the organ at risk, receiving an absorbed dose of 0.074 mGy/MBq, while significant decreases in liver uptake and absorbed doses were observed during SARM therapy, suggesting potential changes in tumor response over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. McCall, KC., Liu, M., Cheng, SC., et al.[2023]

The newly synthesized 11 beta-fluoro-5 alpha-dihydrotestosterone (11 beta-F-DHT) shows high binding affinity to androgen receptors and favorable in vivo properties for prostate cancer imaging, with significant prostate uptake and low bone uptake, making it a promising candidate for diagnostic applications.

In contrast, 11 beta-fluoro-19-nor-5 alpha-dihydrotestosterone (11 beta-F-19-nor-DHT) has the highest binding affinity but demonstrates poor prostate uptake and rapid metabolism in vivo, indicating that structural differences significantly impact the biodistribution and effectiveness of these imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Choe, YS., Lidström, PJ., Chi, DY., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic assessment of the uptake of 16beta-18F-fluoro-5alpha-dihydrotestosterone (FDHT) in prostate tumors as measured by PET. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Sensitivity of 18F-fluorodihydrotestosterone PET-CT to count statistics and reconstruction protocol in metastatic castration-resistant prostate cancer. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Androgen Receptor Imaging in the Management of Hormone-Dependent Cancers with Emphasis on Prostate Cancer. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Positron tomographic assessment of androgen receptors in prostatic carcinoma. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

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]

8. United States pubmed.ncbi.nlm.nih.gov

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]