Serial Imaging of the Novel Radiotracer [^18F] FLuorthanatrace ([^18F] FTT) by PET/CTF

PRIMARY OBJECTIVES:

\- Evaluate fluorine F 18 fluorthanatrace (\[18F\]Fluorthanatrace) positron emission tomography/computed tomography (PET/CT) as an imaging biomarker of poly \[ADP-ribose\] polymerase (PARP)-1 activity in 3 cohorts of cancer patients: 1) ovarian, fallopian tube, primary peritoneal 2) breast cancer, and 3) non-ovarian, non-breast solid tumor.

SECONDARY OBJECTIVES:

* Evaluate the safety of \[18F\]Fluorthanatrace.
* Correlate \[18F\]Fluorthanatrace uptake measures with BRCA mutation status.
* Correlate \[18F\]Fluorthanatrace uptake measures with poly \[ADP-ribose\] polymerase (PARP-1) activity in tumor tissue samples in patients who undergo biopsies.
* Evaluate change in \[18F\]Fluorthanatrace uptake measures after therapy initiation with repeat imaging before and after treatment initiation.
* To confirm the variability of imaging findings from repeated \[18F\]FTT PET/CT over 1 week before treatment initiation
* Determine the change in \[18F\]FluorThanatrace uptake before treatment initiation and at time of clinical progression
* Correlate \[18F\]FluorThanatrace uptake at time of clinical progression measures with genetic reversion mutation status

OUTLINE:

Patients receive fluorodeoxyglucose (FDG) intravenously (IV) and undergo FDG PET/CT scan over 20-30 minutes if they have not already had one per standard of care. At least 20-24 hours later, patients receive fluorine F 18 fluorthanatrace IV and undergo fluorine F 18 fluorthanatrace (\[18F\]FTT) PET/CT over 1 hour.

After completion of study treatment, patients are followed up at 24 hours.

• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography: Undergo FDG PET/CT
• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography: Undergo \[18F\]FTT PET/CT
• Fludeoxyglucose F-18 (Radiation), also known as 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18: Given IV
• Fluorine F 18 Fluorthanatrace (Radiation), also known as [18F]FluorThanatrace, [18F]FTT: Given IV
• Positron Emission Tomography (Procedure), also known as Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging: Undergo FDG PET/CT
• Positron Emission Tomography (Procedure), also known as Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging: Undergo \[18F\]FTT PET/CT

Primary outcomes

• Poly (ADP-ribose) polymerase inhibitor (PARP)-1 activity as assessed by fluorine F 18 fluorthanatrace positron emission tomography/computed tomography [Up to 4 years]: Data will be generated for semi-parametric uptake of both tracers by patient and by lesion as well as by PARP activity, and summarized as mean and standard deviation (SD) across patients. For patients for whom tumor tissue is saved, the correlation of uptake values and PARP activity as assayed from biopsy specimens will be measured using the rank correlation (Spearman's rho), and test for significance compared to no correlation.

Secondary outcomes

• Incidence of adverse events [Up to 4 years]
• BRCA mutation status [Up to 4 years]: To determine any correlation with BRCA status, fluorine F 18 fluorthanatrace (\[18F\]FTT) uptake values (mean and SD) across patient and lesion (summing across lesions) will be summarized, by BRCA status group. Group difference will be tested using t-tests.
• PARP-1 activity in tumor tissue samples [Up to 4 years]: Data will be generated for semi-parametric uptake of both tracers by patient and by lesion as well as by PARP activity, and summarized as mean and SD across patients. For patients for whom tumor tissue is saved, the correlation of uptake values and PARP activity as assayed from biopsy specimens will be measured using the rank correlation (Spearman's rho), and test for significance compared to no correlation.
• Change in fluorine F 18 fluorthanatrace uptake measures after therapy [Baseline up to 4 years]

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* History of known or suspected solid tumor.
* At least one lesion ≥ 1.0 cm that is seen on standard imaging (e.g. computed tomography \[CT\], magnetic resonance imaging \[MRI\], ultrasound, fludeoxyglucose \[FDG\] PET/CT).

Exclusion Criteria:

* Females who are pregnant or breast feeding at the time of screening will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential < 2 weeks prior to screening as standard of care.
* Inability to tolerate imaging procedures in the opinion of an investigator or treating physician.
* Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study.

• Results publication: Lin LL, Wong F, Lin R, Yap T, Litton JK. Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib. JCO Precis Oncol. 2024 Aug;8:e2400303. doi: 10.1200/PO.24.00303. PMID 39208372

• Lilie L Lin, Principal investigator, M.D. Anderson Cancer Center

NIH grants: R01CA249329