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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how PET scans, which use a small amount of radioactive material, might better detect areas where prostate cancer has spread. It employs two different tracers: [18F] Dihydro-Testosterone (18F-FDHT or 16β-18F-fluoro-5α-dihydrotestosterone) and [18F]-Fluoro-2-Deoxy-D-Glucose (FDG or Fluorodeoxyglucose F 18), to enhance cancer visibility. Men diagnosed with prostate cancer who show signs of disease progression, such as new spots on bone scans or rising PSA levels, might be suitable candidates. The trial aims to improve cancer spread detection, aiding in better treatment planning. As an unphased trial, it offers a unique opportunity to advance cancer detection methods.

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 prior data suggests that these PET imaging techniques are safe for prostate cancer patients?

Research has shown that [18F] Dihydro-Testosterone (FDHT) helps visualize prostate cancer. Early results indicate it is generally well-tolerated in clinical settings, with no major side effects reported. This is encouraging for those considering trials using this tracer.

Similarly, [18F]-Fluoro-2-Deoxy-D-Glucose (FDG) is another imaging agent with a strong history. The FDA has already approved it for other uses, confirming its well-known safety. Studies have shown it is generally safe, with few reports of serious side effects.

Both [18F] FDHT and [18F] FDG have shown promise in imaging studies and maintain good safety records. These findings may reassure those considering trial participation about the safety of these imaging agents. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using [18F] Dihydro-Testosterone and [18F]-Fluoro-2-Deoxy-D-Glucose for prostate cancer because these substances offer a unique way to visualize cancer activity. Unlike traditional treatments that might target the cancer cells directly, these compounds are used in PET imaging to provide detailed insights into how prostate cancer metabolizes testosterone and glucose. This imaging technique can give a clearer picture of the cancer's behavior and response to treatment, potentially leading to more personalized and effective treatment plans. By targeting the cancer's metabolic activity, this approach could help tailor therapies to individual patients' needs more precisely than current methods.

What evidence suggests that this trial's imaging techniques could be effective for detecting prostate cancer spread?

Research has shown that FDG PET/CT scans benefit patients with high-risk prostate cancer by detecting aggressive cancer areas that other methods might miss. However, these scans are less effective at identifying slow-growing prostate tumors. In contrast, FDHT scans show promise by quickly identifying prostate cancer through targeting proteins involved in cancer growth. Studies indicate that FDHT PET scans effectively highlight active cancer areas. In this trial, participants will undergo both FDG and FDHT PET imaging, as each method offers different insights, potentially complementing each other in assessing the spread of prostate cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael Morris, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2866076/

Fluoro-5α Dihydrotestosterone (FDHT) in Prostate Tumors ... Two clinical studies subsequently demonstrated successful PET imaging of prostate cancer using 18F-FDHT (4,5,6). These studies showed rapid tumor uptake and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10417772/

FDHT PET for the Imaging of Androgen Receptor in Prostate ... The aim of this systematic review is to provide a comprehensive overview of the role of fluoro-5α-dihydrotestosterone ([ 18 F]-FDHT) for the in vivo imaging of ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/252119

Preclinical comparison of [18F]FDHT and a novel androgen ... Here we report the development of a SARM based AR tracer and its in vitrobinding assays and in vivo evaluation and comparison to [18F]FDHT in a ...

4. mskcc.org mskcc.org/cancer-care/clinical-trials/00-095

Deoxy-D-Glucose (FDG) and [18F] Dihydro-Testosterone ... The primary purpose of this study is to learn how accurately DHT identifies areas of active prostate cancer, compared to standard imaging tests such as bone ...

5. academic.oup.com academic.oup.com/noa/article/3/1/vdab019/6123870

[18F]-FDHT PET/CT as a tool for imaging androgen receptor ... 16β-18F-fluoro-5α-dihydrotestosterone ([18F]-FDHT) is a positron emission tomography (PET) tracer used to detect AR expression in prostate and ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/jnumed/59/10/1516.full.pdf

Castration-Resistant Prostate Cancer Metastases The aim of this study was to prospectively assess repeatability and reproducibility of whole-body 18F-FDHT uptake metrics of. mCRPC metastases.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804920313319

FDHT-PET to predict bicalutamide efficacy in patients with ... In this feasibility study, a bicalutamide-induced reduction in [ 18 F]-FDHT uptake could be detected by follow-up [ 18 F]-FDHT-PET in patients with AR + MBC.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4530021/

Fully-automated synthesis of 16β-18F-fluoro-5α ... ... tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00588185

Study Details | NCT00588185 | [18F]-Fluoro-2-Deoxy-D- ... FDHT is targeted to the AR and has been shown in preliminary studies to visualize prostate cancers in man. This study will apply our established methods to ...