FLT PET Imaging for Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Barbara Ann Karmanos Cancer Institute

Disqualifiers: Pregnancy, Nursing, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

80 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Diagnostic procedures, such as 3'-deoxy-3'-\[18F\] fluorothymidine (FLT) PET imaging, may help find and diagnose cancer. It may also help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This phase I trial is studying FLT PET imaging in patients with cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug 3'-deoxy-3'-[18F]fluorothymidine (FLT) for cancer treatment?

Research shows that FLT is effective in imaging cell proliferation, which helps monitor early responses to cancer treatments like radiation and chemotherapy. It has been used to assess tumor activity in various cancers, including lung and prostate cancer, and to distinguish between tumor recurrence and tissue damage in brain tumors. ^{1 2 3 4 5}

Is FLT PET imaging safe for humans?

A study sponsored by the National Cancer Institute found that the dose of FLT used for imaging does not produce significant toxicity, suggesting it is generally safe for humans. ^{1 3 6 7 8}

How is FLT PET imaging different from other cancer treatments?

FLT PET imaging is unique because it uses a special tracer, 3'-deoxy-3'-[18F]fluorothymidine (FLT), to non-invasively assess how fast cancer cells are growing by tracking cell proliferation. This approach helps in early detection of how well a cancer treatment is working, unlike traditional methods that may not show changes as quickly. ^{1 3 5 8 9}

Research Team

Anthony F. Shields

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

This trial is for patients with confirmed solid tumors or blood cancers, who are awaiting biopsy or surgery. They must be able to lie still in a PET scanner and fit within its dimensions. Pregnant or nursing women cannot participate, and those who can have children must use effective birth control.

Inclusion Criteria

My cancer was confirmed through a tissue sample.

I am waiting for a biopsy or surgery to examine a detected mass.

I can stay still during a PET scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo up to four 3'-deoxy-3'-[18F] fluorothymidine positron emission tomography imaging procedures to measure tumor proliferation and the DNA synthetic pathway

2 hours per imaging session

Up to 4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

Treatment Details

Interventions

• 3'-deoxy-3'-[18F]fluorothymidine

Trial Overview The study is examining the effectiveness of FLT PET imaging in detecting cancer and predicting treatment response. This phase I trial aims to determine how well this diagnostic procedure works for various types of cancer.

Participant Groups

Group I: 3'-deoxy-3'-[18F]fluorothymidine Experimental Treatment 1 Intervention

The PET scan data collection is started immediately and is continued for 2 hours. This procedure will measure tumor growth within the body.

Who Is Running the Clinical Trial?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The study demonstrated that the PET tracer (18)F-FLT shows significantly higher uptake in lung cancer tissues compared to normal tissues, allowing for clear imaging of tumors in a murine model.

(18)F-FLT uptake was strongly correlated with tumor cell proliferation, as indicated by the positive rate of PCNA, making it a promising tool for assessing cancer growth, unlike (18)F-FDG which showed no such correlation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Correlation of 3'-deoxy-3'-18F-fluorothymidine uptake to cell proliferation in lung carcinoma xenografts]. Liu, X., Zhou, NK., Zhang, JM., et al.[2016]

In a study involving 19 patients (15 with tumor recurrence and 4 with radionecrosis), the metabolic flux (K (FLT)) from 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) PET scans was effective in distinguishing between glioma recurrence and radionecrosis, outperforming traditional imaging methods.

The study found that K (FLT) and the phosphorylation rate (k (3)) were significant indicators for differentiating the two conditions, while standard uptake values and visual analyses of both [18F]FLT and FDG PET scans did not show significant differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NCI-sponsored trial for the evaluation of safety and preliminary efficacy of 3'-deoxy-3'-[18F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: preliminary efficacy studies. Spence, AM., Muzi, M., Link, JM., et al.[2022]

In a study using C3H/HeN mice with squamous cell carcinomas, FLT PET imaging showed a significant reduction in tumor uptake 24 hours after radiation treatment, indicating its potential as an effective tool for monitoring early responses to radiation therapy.

Unlike FLT, FDG PET imaging did not show significant changes in tumor uptake after radiation, suggesting that FLT may provide more sensitive insights into the effects of radiation on tumor proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors. Yang, YJ., Ryu, JS., Kim, SY., et al.[2018]

The study demonstrated that 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is effective for detecting prostate cancer in a mouse model, showing the highest uptake in tumors at 2 hours post-injection, which indicates its potential as a reliable imaging agent.

(18)F-FLT can also monitor the therapeutic effects of androgen ablation therapy, as evidenced by a significant reduction in tracer uptake in tumors following treatment, correlating with actual tumor size changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. Oyama, N., Ponde, DE., Dence, C., et al.[2019]

The experimental chemotherapeutic agent TP202377 significantly inhibited cell proliferation in sensitive A2780 ovarian cancer tumors, as shown by a 46% decrease in [18F]FLT uptake at 6 hours post-treatment, indicating its efficacy in this model.

In contrast, TP202377 did not affect tumor growth or [18F]FLT uptake in resistant A2780/Top216 and SW620 colon cancer models, demonstrating the potential for [18F]FLT PET to non-invasively differentiate between sensitive and resistant tumors shortly after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FLT PET for non-invasive assessment of tumor sensitivity to chemotherapy: studies with experimental chemotherapy TP202377 in human cancer xenografts in mice. Munk Jensen, M., Erichsen, KD., Björkling, F., et al.[2021]

In a study involving 12 patients with gliomas, the administration of 3'-[F-18]Fluoro-3'-deoxythymidine (FLT) at a dose of 0.07 mCi/kg showed no significant toxicity, indicating its safety for imaging purposes.

The amount of FLT used for imaging was extremely low, only 0.0001% to 0.0009% of the least toxic cumulative dose previously tested in clinical trials, reinforcing its safety as a radiotracer for assessing cellular proliferation in cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NCI-sponsored trial for the evaluation of safety and preliminary efficacy of FLT as a marker of proliferation in patients with recurrent gliomas: safety studies. Spence, AM., Muzi, M., Link, JM., et al.[2021]

The study demonstrated that [18F]3'-deoxy-3'-fluorothymidine (FLT) can effectively measure tumor proliferation with PET imaging, showing that 74% of blood activity remains unmetabolized after 60 minutes, which is crucial for accurate imaging.

Using only eight venous blood samples for kinetic analysis and one sample at 60 minutes for metabolite analysis can provide reliable data, significantly reducing the number of samples needed for assessing FLT retention and metabolic rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention. Shields, AF., Briston, DA., Chandupatla, S., et al.[2018]

The experimental chemotherapy Top216 significantly inhibited tumor growth in human ovary cancer xenografts in mice, with a notable decrease in cell proliferation observed as early as 2 hours after treatment, as measured by the (18)F-FLT PET scans.

(18)F-FLT PET imaging proved to be a promising method for early, non-invasive assessment of chemotherapy effects, allowing for timely evaluation of treatment responses before changes in tumor size are detectable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. Jensen, MM., Erichsen, KD., Björkling, F., et al.[2021]

The PET imaging agent 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is effective for studying cellular proliferation in cancers, with radiation dosimetry estimates showing it is safe for use in patients.

The highest radiation dose from (18)F-FLT is absorbed by the bladder, but overall radiation risks are comparable to other nuclear medicine tests and are within accepted safety limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Fluorothymidine radiation dosimetry in human PET imaging studies. Vesselle, H., Grierson, J., Peterson, LM., et al.[2016]

References

1. China pubmed.ncbi.nlm.nih.gov

[Correlation of 3'-deoxy-3'-18F-fluorothymidine uptake to cell proliferation in lung carcinoma xenografts]. [2016]

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

NCI-sponsored trial for the evaluation of safety and preliminary efficacy of 3'-deoxy-3'-[18F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: preliminary efficacy studies. [2022]

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

Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors. [2018]

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

Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. [2019]

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

[18F]FLT PET for non-invasive assessment of tumor sensitivity to chemotherapy: studies with experimental chemotherapy TP202377 in human cancer xenografts in mice. [2021]

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

NCI-sponsored trial for the evaluation of safety and preliminary efficacy of FLT as a marker of proliferation in patients with recurrent gliomas: safety studies. [2021]

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

A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention. [2018]

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

Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. [2021]

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

18F-Fluorothymidine radiation dosimetry in human PET imaging studies. [2016]