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\[18F\]FluorThanatrace is a radiotracer for PET/CT

[18F]FluorThanatrace

Elizabeth McDonald, MD

Up to 30 evaluable participants with known or suspected breast cancer (BIRADS 5 by imaging) will undergo FTT PET/CT imaging before primary surgery or neoadjuvant therapy. Patients undergoing neoadjuvant therapy may choose to have a second FTT PET/CT scan after the start of therapy (1 days to 3 weeks). FTT PET/CT uptake will be correlated with pathology measures and treatment response, in subjects undergoing neoadjuvant therapy

Evaluating in Vivo PARP-1 Expression With 18F-FluorThanatrace Positron Emission Tomography (PET/CT) in Breast Cancer

Abramson Cancer Center at Penn Medicine

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Radiopharmaceuticals

Gleason 9 or oligometastic disease (n=10)

Fluorine-18 labeled FluorThanatrace \[18F\]FTT can be synthesized with high specific activity so the quantity of mass injected with the radiopharmaceutical is \< 10 μg.

Poly(ADP-ribose) polymerase (PARP) is a family of enzymes involved in base excision repair (the repair of DNA single-strand breaks) and alternative end joining (repair of DNA double-strand breaks). The molecular basis of PARP1 inhibitor function may depend on the dual roles of PARP1 as a modulator of gene transcription in addition to DNA damage repair 3.

Poly(ADP Ribose) Polymerase 1

Dan Pryma, MD

Men with a history of prostate cancer may be in this study. Subjects recommended for a prostatectomy or oligometastectomy will undergo PET/CT imaging using a novel radiotracer \[18F\]FTT to evaluate PARP-1 activity in known or suspected sites of primary or metastatic disease. Imaging will be compared with pathology results, including additional research assays when possible.

Evaluating in Vivo PARP-1 Expression With 18F-FluorThanatrace Positron Emission Tomography (PET/CT) in Prostate Cancer

Fluorodeoxyglucose F18

Twelve participants with cancer and eight healthy volunteers will be recruited first to undergo whole-body PET/CT imaging to determine the whole body dosimetry of \[18F\]FluorThanatrace.

An additional 30 participants with cancer will undergo a 1-hour dynamic scan upon injection of \[18F\]FluorThanatrace to determine the kinetics of the tracer in tumors to correlate with tissue-based markers of PARP activity and to obtain metabolite information to help determine the best quantification approach for the PET images. When possible these subjects will also undergo 18F-FDG imaging for comparison to tumor metabolism

For the Dosimetry Studies, 10 mCi of \[18F\]FTT will be injected intravenously, and participants will be placed in the following groups to be imaged with PET at the specified time points: 0 minute group--image at 0 and 120 min. after tracer injection; 30 minute group--image at 30 and 150 min. after tracer injection; 60 minute group--image at 60 and 180 min. after tracer injection; and 90 minute group--image at 90 and 210 min. after tracer injection.

For the Kinetic Studies, 10 mCi of \[18F\]FTT will be injected intravenously, and a 60-minute dynamic PET scan will be obtained starting at the time of injection.

Farrokh L Dehdashti, MD

The purpose of this research study is to determine the feasibility of using positron emission tomography (PET) imaging technology to image cancer with \[18F\]FluorThanatrace (\[18F\]FTT), a new radioactive tracer compound that has been developed that images poly(ADP-ribose) polymerase 1 (PARP-1) activity.

Poly(ADP-ribose) polymerase 1 (PARP1) is a deoxyribonucleic acid (DNA) repair enzyme that enables normal cell survival as well as certain cancers. Pharmaceutical companies have invested heavily in PARP1 inhibitor development because these agents can effectively treat certain cancers as single agents, thus sparing those patients from chemotherapy toxicities. However, clinical trials testing PARP1 inhibitors have demonstrated mixed results due to the inability to measure the degree of PARP1 inhibition in tumors reliably. Accurately measuring tumoral PARP1 activity levels before and after PARP1 inhibitor treatment will: (1) enable identification of patients whose tumors exhibit PARP activity and are therefore good candidates for PARP inhibitor therapy, and (2) confirm that adequate doses of PARP1 inhibitors are being administered to patients, thus improving dose selection for further study in clinical trials. Thus, noninvasive approaches for measuring tumoral PARP1 activity would have commercialization potential in not only supporting development of PARP1 inhibitors but also after Food and Drug Administration (FDA) approval to assess clinical PARP1 inhibitor treatment responses.

Inflammation also contributes to a number of diseases involving the lungs and other organs. Increasing evidence suggests that PARP1 may also play a central role in modulating immune inflammatory responses. Thus, the data from this trial will also be used to develop this approach for studying lung inflammatory responses.

A new radiolabeled compound, \[18F\]FluorThanatrace (\[18F\]FTT), has been generated which can be used to measure PARP1 activity noninvasively and quantitatively using positron emission tomography (PET). Our data in cancer models show that the uptake of our compound is specific for PARP1 activity and correlates with biochemically determined PARP1 activity. Additional preliminary data also suggests that decreased \[18F\]FTT uptake predicts tumor response to PARP inhibition with olaparib, a PARP1 inhibitor currently being evaluated in clinical trials. Therefore, the investigators are conducting this Phase 0 trial to develop \[18F\]FTT for clinical use in cancer patients.

To date, no biomarkers have been developed beyond genetic testing for breast cancer 1 and 2 (BRCA1/2) mutations that can aid in patient selection for treatment with PARP inhibition. Moreover, no technologies are available to monitor the efficacy of PARP inhibition. Our technology provides both a biomarker for patient selection as well as a means of monitoring PARP activity during treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluating in Vivo PARP-1 Expression With 18F-FluorThanatrace Positron Emission Tomography (PET/CT) in Breast Cancer	NCT03083288	Breast Cancer	[18F]FluorThana...	18 Years -	Abramson Cancer Center at Penn Medicine
Evaluating in Vivo PARP-1 Expression With 18F-FluorThanatrace Positron Emission Tomography (PET/CT) in Prostate Cancer	NCT03334500	Prostate Cancer	[18F]FluorThana... Poly(ADP Ribose...	18 Years -	Abramson Cancer Center at Penn Medicine
PET Imaging of PARP Activity in Cancer	NCT02469129	Cancer	[18F]FluorThana...	18 Years -	Washington University School of Medicine
PET Imaging of PARP Activity in Cancer	NCT02469129	Cancer	[18F]FluorThana...	18 Years -	Washington University School of Medicine
PET Imaging of PARP Activity in Cancer	NCT02469129	Cancer	[18F]FluorThana...	18 Years -	Washington University School of Medicine

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