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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new PET scan technique in identifying specific signs in cancer cells. It uses a special tracer, 11C-YJH08, to highlight glucocorticoid receptors, which may cause cancer cells to resist certain treatments. The study aims to enhance detection during treatment, potentially leading to better therapies. Individuals with any type of metastatic cancer, especially those with prostate cancer unresponsive to hormone therapy, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new approach.

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 prior data suggests that PET imaging using 11C-YJH08 is safe for detecting cell receptor expression in metastatic cancer?

Research shows that 11C-YJH08 remains under study to assess its safety in humans. This new treatment is in the early testing stages. Current studies have not reported harmful effects, but these results are preliminary. As a radiotracer, it helps doctors see certain conditions more clearly in scans. In this first phase of trials, the primary goal is to determine if it is safe and well-tolerated by patients. More information is needed to confirm its safety. Participants should discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 11C-YJH08 because it offers a novel approach to imaging cancerous tumors. Unlike traditional PET scans that use other tracers, 11C-YJH08 targets specific tumor markers, potentially providing more precise images of metastases. This can lead to better detection and monitoring of tumor spread, especially in solid tumors and metastatic castration-resistant prostate cancer (CRPC). The precision of this tracer could improve treatment planning, making it a significant advancement over conventional imaging techniques.

What evidence suggests that PET imaging using 11C-YJH08 is effective for detecting glucocorticoid receptor expression in metastatic cancer?

Research has shown that 11C-YJH08 helps doctors visualize certain receptors on tumor cells using PET scans. This special substance attaches to receptors that can increase when patients receive specific treatments. By identifying these changes, doctors might detect tumors that could resist hormone treatments. In this trial, participants in Cohort A, Cohort B, and Cohort C will receive 11C-YJH08 to highlight these receptors, providing a clear view of their location. Early studies demonstrated that 11C-YJH08 effectively highlights these receptors, potentially leading to better treatment plans by targeting these receptors with specific therapies. ^{1 2 5 6 7}

Who Is on the Research Team?

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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.

Hemoglobin >= 8.0 g/dL

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8844266/

11C-YJH08 PET - PMC Here, we report evidence supporting translational studies with (±)-11C-5-(4-fluorobenzyl)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4 ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/62/5/723

11C-YJH08 PET | Journal of Nuclear Medicine (±)- 11 C-YJH08 was synthesized by reaction of the phenolic precursor with 11 C-methyl iodide, giving a radiochemical yield of 51.7% ± 4.7%.

3. jnm.snmjournals.org jnm.snmjournals.org/content/jnumed/62/5/723.full.pdf

The Synthesis and Structural Requirements for Measuring ... supporting translational studies with (±)-11C-5-(4-fluorobenzyl)-10- methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]-quinoline. ((±)-11C-YJH08), a ...

4. researchgate.net researchgate.net/publication/340498804_A_Novel_Radioligand_Reveals_Tissue_Specific_Pharmacological_Modulation_of_Glucocorticoid_Receptor_Expression_with_Positron_Emission_Tomography

(PDF) A Novel Radioligand Reveals Tissue Specific ... Here, we report evidence supporting translational studies with (±)-11C-5-(4-fluorobenzyl)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4 ...

5. researchgate.net researchgate.net/figure/Fig-10-Radiosyntheis-of-C-11-labeled-camptothecin-derivatives-by-N-11-Cmethylation_fig1_43133198

Radiosyntheis of C-11 labeled camptothecin derivatives by ... Here, we report evidence supporting translational studies with (±)-11C-5-(4-fluorobenzyl)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]-quinoline (( ...

6. escholarship.org escholarship.org/content/qt5ss897s4/qt5ss897s4_noSplash_1c87d2a572bdf68f5082e5e7ae604a81.pdf

11C- YJH08 PET supporting translational studies with (±)-11C-5-(4-fluorobenzyl)-10- methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]-quinoline. ((±)-11C-YJH08), a ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/jnumed/early/2020/09/04/jnumed.120.249755.full.pdf

11C-YJH08 PET PERTINENT FINDINGS: We synthesized 11C-5-(4-fluorobenzyl)-10-methoxy-2,2,4-trimethyl-. 2,5-dihydro-1H-chromeno[3,4-f]quinoline (11C-YJH08) a ...