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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging technique, FLT PET, to improve cancer detection and diagnosis. The aim is to determine if this imaging can better predict a patient's response to cancer treatment and assist doctors in planning the best treatment approach. Participants should have a confirmed solid tumor or blood cancer or be awaiting a biopsy or surgery for a suspected cancer mass. The trial requires participants to lie still in a PET scanner for the imaging process. As a Phase 2 trial, this research measures the effectiveness of the imaging technique in an initial, smaller group, offering participants a chance to contribute to advancements in cancer diagnostics.

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 prior data suggests that FLT PET imaging is safe for cancer patients?

Research has shown that a substance called FLT is used in PET scans to help doctors observe cancer growth. Studies have found that small amounts of FLT in these scans do not cause harm. Specifically, patients experienced no adverse reactions or side effects from the FLT injected into their veins. This indicates that FLT is safe and well-tolerated for imaging, making it a promising tool for diagnosing and planning cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for cancer that primarily focus on directly attacking tumor cells, 3'-deoxy-3'-[18F]fluorothymidine (FLT) offers a unique approach by using PET imaging to measure tumor growth. This method harnesses the power of advanced imaging to provide real-time insights into how fast a tumor is growing, potentially offering a more precise and dynamic understanding of cancer progression. Researchers are excited because FLT PET imaging could revolutionize how we monitor the effectiveness of cancer treatments, enabling personalized treatment plans that are more responsive to how an individual's cancer is behaving.

What evidence suggests that FLT PET imaging is effective for diagnosing cancer?

Research has shown that a special type of PET scan, called FLT PET imaging, holds promise for diagnosing and monitoring cancer. Studies have found that FLT is absorbed by cancer cells and integrates into their DNA, serving as a useful marker for tumor growth. In lung cancer, FLT helps determine the cancer stage and evaluate treatment effectiveness. It may also predict a patient's response to therapy. Early findings suggest that FLT PET imaging can reliably measure the rate of cancer cell multiplication. Participants in this trial will undergo FLT PET imaging to assess tumor growth within the body. ^{1 3 4 6 7}

Who Is on the Research Team?

Anthony F. Shields

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Are You a Good Fit for This Trial?

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

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

I can stay still during a PET scan.

Not pregnant or nursing

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8253862/

Clinical value of 3'-deoxy-3'-[18F]fluorothymidine-positron ... This review summarises and evaluates published studies on the clinical use of [ 18 F]FLT to diagnose, stage and assess response to therapy in lung cancer.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK23373/

Deoxy-3'-[18F]fluorothymidine - NCBI - NIH These results demonstrate the cellular uptake, intracellular trapping, and incorporation into the DNA of [18F]FLT in pancreatic cancer cells in ...

3. thno.org thno.org/v07p0040.htm

Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic ... These preclinical data indicate that [ 18 F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies.

4. aacrjournals.org aacrjournals.org/cancerres/article/63/13/3791/510100/3-Deoxy-3-18F-Fluorothymidine-as-a-New-Marker-for

18F]Fluorothymidine as a New Marker for Monitoring Tumor ... 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) has been proposed as a new marker for imaging tumor proliferation by positron emission tomography (PET).

5. bmcmedphys.biomedcentral.com bmcmedphys.biomedcentral.com/articles/10.1186/1471-2385-7-3

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F ... The potential impact of 18F-FLT on tumor imaging is two-fold: first, tumor proliferation is a prognostic factor for certain tumor types (e.g. ...

6. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/flt-ib.pdf

Investigator's Brochure: [F-18]FLT 3'-deoxy-3'-[F-18]fluorothymidine: [F-18]FLT (MW 243) is a structural analog of the DNA constituent, thymidine (Figure 1). It is a radiolabeled ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666364322001060

Role of 3'-Deoxy-3'-[18F] Fluorothymidine Positron ... This imaging substudy of the dose-expansion TRAP study aimed to assess tumor proliferation as a marker of treatment response in MPM and NSCLC to ADIPemCis. We ...