PET Imaging for Cancer

Overseen By Khadija Siddiqua

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Rahul Aggarwal

Must not be taking: Systemic glucocorticoids

Disqualifiers: Adrenal insufficiency, Cushing's disease, others

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

Compensation: Varies

Number of Visits: 1

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies if positron emission tomography (PET) imaging using 11C-YJH08 can be useful for detecting certain cell receptor expression in tumor cells in patients with cancer that has spread to other parts of the body (metastatic). 11C-YJH08 is a small-molecule radiotracer that binds to receptors on cells (glucocorticoid receptor) so that they show up better on the PET scan. Systemic therapy (including enzalutamide) can cause more glucocorticoid receptors to be produced in tumor cells, which can make the tumor cells resist hormone therapies. If researchers can find a better way to detect whether glucocorticoid receptors are increasing during therapy, it may lead to more successful therapies using glucocorticoid receptor antagonists.

Will I have to stop taking my current medications?

If you are currently taking systemic glucocorticoids, you will need to stop them at least 7 days before starting the trial.

What data supports the effectiveness of the drug 11C-YJH08 for cancer treatment?

Research on similar compounds, like carbon-11-labeled chromen-4-one derivatives, shows potential for imaging DNA repair enzymes in cancer, which could help in assessing treatment effectiveness. Additionally, studies on EGFR-targeted imaging agents suggest that such compounds can aid in evaluating tumors, potentially supporting the use of 11C-YJH08 in cancer imaging. ^{1 2 3 4 5}

How is the drug used in PET Imaging for Cancer different from other cancer imaging drugs?

The drug used in PET Imaging for Cancer, [(18)F]fluorocholine, is unique because it allows for rapid whole-body imaging with high tumor-to-background contrast, making it effective for detecting various cancers, including those in the brain, which can be challenging with other imaging agents. ^{6 7 8 9 10}

Research Team

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with metastatic castration-resistant prostate cancer, currently on or planning to start treatments like enzalutamide. They must have a good performance status, controlled testosterone levels (if not surgically removed), and normal organ function. Excluded are those with certain medical conditions, recent glucocorticoid use, adrenal insufficiency, inability to consent, or contraindications to MRI.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have prostate cancer resistant to standard treatment and haven't started new medication yet.

I am 18 years old or older.

Exclusion Criteria

Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures

I am unable to give informed consent due to my age, health, or mental condition.

I take steroids for adrenal insufficiency.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosimetry

Participants receive 11C-YJH08 intravenously and undergo PET/MRI or PET/CT to establish dosimetry

1 day

1 visit (in-person)

Imaging and Assessment

Participants undergo PET/MRI or PET/CT at baseline and at time of progression to assess glucocorticoid receptor expression

Up to 24 months

Multiple visits (in-person) as needed

Follow-up

Participants are monitored for safety and effectiveness after imaging

Up to 24 months

Treatment Details

Interventions

• 11C-YJH08

Trial Overview The study tests if PET imaging using the radiotracer 11C-YJH08 can better detect glucocorticoid receptor expression in tumors of patients whose prostate cancer has spread. This could help identify resistance to hormone therapies and improve treatment strategies.

Participant Groups

Group I: Cohort C: Solid Tumor Malignancy Experimental Treatment 5 Interventions

Participants with any solid tumor malignancies other than prostate adenocarcinoma with one or more metastases on conventional imaging will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.

Group II: Cohort B: Metastatic CRPC Experimental Treatment 5 Interventions

Participants with metastatic CRPC will receive approximately 20 mCi of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline and optional repeat scan at the time of progression.

Group III: Cohort A: Any Solid Tumor (Dosimetry Cohort) Experimental Treatment 5 Interventions

Participants with any solid tumor malignancy with evidence of one or more metastases will receive approximately 20 millicurie (mCi) of 11C-YJH08 IV over 1-2 minutes and 10-60 minutes later, undergo either PET/MRI or PET/CT over 90 minutes at baseline.

Who Is Running the Clinical Trial?

Rahul Aggarwal

Lead Sponsor

Trials

13

Recruited

550+

Michael Evans

Lead Sponsor

Trials

1

Recruited

30+

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a pilot study of 21 patients with advanced non-small cell lung cancer (NSCLC), higher baseline uptake of the PET imaging biomarker (11)C-PD153035 was strongly correlated with improved overall survival (OS) and progression-free survival (PFS) when treated with the EGFR inhibitor erlotinib.

The study suggests that (11)C-PD153035 PET/CT could be a useful noninvasive tool for identifying NSCLC patients likely to benefit from EGFR-targeted therapy, although it was not effective for monitoring treatment response over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging with 11C-PD153035 PET/CT predicts survival in non-small cell lung cancer treated with EGFR-TKI: a pilot study. Meng, X., Loo, BW., Ma, L., et al.[2018]

The novel radiotracer [18F]FED20 effectively binds to the epidermal growth factor receptor (EGFR) and shows higher retention in non-small cell lung carcinoma (NSCLC) cells with active mutant EGFR, indicating its potential for targeted imaging in cancer treatment.

Unlike other cyanoquinolines, [18F]FED20 does not interact with ABC transporters, which are known to cause drug resistance, making it a promising candidate for improving patient selection for EGFR-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of ABC Transporter Interaction of a Novel Cyanoquinoline Radiotracer and Implications for Tumour Imaging by Positron Emission Tomography. Slade, RL., Pisaneschi, F., Nguyen, QD., et al.[2021]

The carbon-11 labeled (R)-[11C]PAQ PET imaging biomarker showed a significant reduction in tumor uptake after treatment with a combination of anti-VEGFA antibody and paclitaxel, indicating its potential to evaluate anticancer drug efficacy in preclinical models.

MRI results demonstrated a significant decrease in tumor volume in the combination treatment group, suggesting that (R)-[11C]PAQ may correlate with therapeutic response, although further studies are needed to validate its use as a predictive radiotracer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment response assessment with (R)-[11CPAQ PET in the MMTV-PyMT mouse model of breast cancer. Tegnebratt, T., Lu, L., Eksborg, S., et al.[2022]

New carbon-11-labeled chromen-4-one derivatives were developed as potential PET imaging agents for the DNA repair enzyme DNA-PK in cancer, which could help in understanding cancer biology and treatment responses.

The synthesis of these tracers achieved radiochemical yields of 40-60% and high specific activity (185-370 GBq/μmol), indicating their potential effectiveness for use in PET imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer. Gao, M., Wang, M., Miller, KD., et al.[2015]

A new imaging agent, 99mTcN-MAG3-ADMQ, was developed to target the overexpressed epidermal growth factor receptor (EGFR) in various cancers, showing high radiochemical purity and stability for effective tumor imaging.

In tests on tumor-bearing mice, 99mTcN-MAG3-ADMQ demonstrated significant tumor accumulation and favorable tumor-to-muscle and tumor-to-blood ratios, indicating its potential as a promising radiotracer for SPECT imaging of tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel [99mTcN]2+ labeled EGFR inhibitors as potential radiotracers for single photon emission computed tomography (SPECT) tumor imaging. Zhao, M., Ning, H., Feng, M., et al.[2021]

The study found that [(18)F]Fluorocholine ([(18)F]FCH) is metabolized similarly to [(14)C]choline in glioma cells and tumors, indicating its potential as a reliable imaging agent for tumor detection.

However, the presence of the radiofluorine atom in [(18)F]FCH leads to subtle differences in its biodistribution and metabolism, particularly in hypoxic conditions, which could affect the interpretation of PET imaging results in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodisposition and metabolism of [(18)F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats. Bansal, A., Shuyan, W., Hara, T., et al.[2021]

(18)F-labelled choline derivatives, particularly (18)F-fluorocholine, are effective for detecting local and metastatic prostate cancer, providing a reliable single-step examination for patients with recurrent biochemical prostate cancer.

While (18)F-fluorocholine PET shows excellent discrimination between tumor and normal tissue in the brain, its utility in liver cancer detection is more challenging due to higher physiological uptake in normal liver tissue, although it remains promising for identifying hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature. Mertens, K., Slaets, D., Lambert, B., et al.[2021]

The study suggests that [18F]fluorophenylalanine (18F-Phe) is a promising alternative to L-[methyl-11C]methionine (11C-Met) for tumor imaging, offering a longer half-life and better contrast in abdominal imaging.

18F-Phe demonstrated similar tumor uptake and response to radiotherapy as 11C-Met, indicating its potential effectiveness in monitoring tumor activity and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of fluorine-18-fluorophenylalanine for tumor imaging compared with carbon-11-L-methionine. Kubota, K., Ishiwata, K., Kubota, R., et al.[2016]

Fluorocholine (FCH), a fluorine-18 labeled choline derivative, shows promise as a PET imaging agent for various cancers, including breast, prostate, liver, and brain tumors.

FCH allows for rapid whole-body imaging within minutes of injection, providing high tumor-to-background contrast, which could enhance the detection of tumors that are difficult to visualize with traditional imaging methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer imaging with fluorine-18-labeled choline derivatives. Kwee, SA., DeGrado, TR., Talbot, JN., et al.[2018]

The study evaluated [(18)F]fluorocholine (FCH) as a promising PET imaging probe for cancer detection, showing effective phosphorylation rates similar to choline in vitro, particularly in prostate cancer cells.

Preliminary PET imaging in patients indicated that FCH successfully highlighted cancerous tissues in prostate and breast cancers, as well as in a recurrent brain tumor, suggesting its potential as a reliable oncologic probe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. DeGrado, TR., Baldwin, SW., Wang, S., et al.[2016]

References

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

Molecular imaging with 11C-PD153035 PET/CT predicts survival in non-small cell lung cancer treated with EGFR-TKI: a pilot study. [2018]

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

Identification of ABC Transporter Interaction of a Novel Cyanoquinoline Radiotracer and Implications for Tumour Imaging by Positron Emission Tomography. [2021]

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

Treatment response assessment with (R)-[11CPAQ PET in the MMTV-PyMT mouse model of breast cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer. [2015]

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

Novel [99mTcN]2+ labeled EGFR inhibitors as potential radiotracers for single photon emission computed tomography (SPECT) tumor imaging. [2021]

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

Biodisposition and metabolism of [(18)F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature. [2021]

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

Feasibility of fluorine-18-fluorophenylalanine for tumor imaging compared with carbon-11-L-methionine. [2016]

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

Cancer imaging with fluorine-18-labeled choline derivatives. [2018]

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

Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. [2016]