Simultaneous Hyperpolarized [1-13C]Pyruvate and 18F-FDG PET/MRS in Cancer Patients

NCT ID: NCT05396118

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-18
• Study Completion Date: 2024-12-31

Brief Summary

Prospective phase 2a clinical trial to demonstrate proof-of-concept for simultaneous hyperpolarized [1-13C]pyruvate and 18F-FDG for positron emission tomography (PET) and MRS (magnetic resonance spectroscopy) in a PET/MR scanner in patients with cancer.

Detailed Description

PET imaging with 18F-FDG is a well established method for non invasively assessing the intracellular glucose accumulation. 18F-FDG PET is used in many applications with diagnosing and staging of patients with cancer being one of the primary indications. Once internalized into the cell, 18F-FDG is phosphorylated to the metabolically inactive 18F-FDG-6-phosphate. Therefore it is not possible to determine what happens to the downstream glucose metabolites. In particular, it is not possible to determine the conversion into lactate, which is upregulated in many cancers. The upregulation of lactate conversion in cancers, even in presence of oxygen, is known as the Warburg effect.

Hyperpolarized [1-13C]pyruvate MRS makes is possible to circumvent this limitation. The technique makes is it possible to follow the downstream fate of the glycolysis intermediate, pyruvate, and in particular makes is is possible to non-invasively and in in real time measure the glycolytic conversion of pyruvate into lactate as a direct measure of the Warburg effect.

When using a PET/MR scanner, it is possible to simultaneous measure the glucose influx with 18F-FDG and the conversion of pyruvate into lactate with hyperpolarized [1-13C]pyruvate. In this way, the two modalities provide complementary information on the in vivo glycose metabolism.

The prospective phase 2a project will include up to 15 patients diagnosed with breast cancer, gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) of all grades (G1, G2, G3)., lymphomas or sarcomas The aim is to demonstrate proof-of-concept for the feasibility of simultaneous acquisition of hyperpolarized [1-13C]pyruvate MRS and 18F-FDG PET imaging in a PET/MR scanner in cancer patients to allow for simultaneous measurements of overall tumor pyruvate-to-lactate conversion parameters on MRS and glucose influx with 18F-FDG on PET.

Included patients are injected with a standard dose of radioactive 18F-FDG. Subsequent dynamic PET acquisition is performed for up to 90 minutes after injection on an area-of-interest covering pre-specified tumor lesion(s). Regional anatomical magnetic resonance imaging (MRI) is performed, including diffusion weighted imaging (DWI) and contrast enhanced imaging (DCE). MRS/MRSI is performed following the injection(s) of hyperpolarized [1-13C]Pyruvate.

When available, resected tumor tissues samples from surgical specimens or biopsies obtained in relation to routine clinical procedures will be collected and analyses of enzymes and markers of glycolytic metabolism will be performed ex vivo and compared with the in vivo data from PET/MRS.

Conditions

Breast Cancer; Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Carcinoma Metastatic; Lymphoma; Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Experimental

Injection of 18F-FDG and injections of hyperpolarized \[1-13C\]Pyruvate and subsequent PET/MRI/MRS scan

Group Type: EXPERIMENTAL

18F-FDG

Intervention Type: DRUG

Injection of 4 MBq/kg of 18F-FDG followed by dynamic positron emission tomography (PET) imaging

Injection of hyperpolarized [1-13C]Pyruvate

Intervention Type: DRUG

Injection of one bolus of 0.43 ml/kg of approximately 250 mM hyperpolarized \[1-13C\]Pyruvate followed by magnetic resonance spectroscopy (MRS) / magnetic resonance spectroscopy imaging (MRSI). After a 5-30 min pause, injection of a second bolus of 0.43 ml/kg of approximately 250 mM hyperpolarized \[1-13C\]Pyruvate followed by MRS / MRSI.

PET/MR/MRS/MRSI scanning

Intervention Type: PROCEDURE

Regional dynamic PET acquisition for up to 90 minutes following 18F-FDG injection is performed focused on a region-of-interest (ROI). Anatomical magnetic resonance imaging (MRI) is performed in the ROI, including diffusion weighted imaging (DWI) and contrast enhanced imaging (DCE). MRS/MRSI is performed following the injections of hyperpolarized \[1-13C\]Pyruvate.

Interventions

18F-FDG

Injection of 4 MBq/kg of 18F-FDG followed by dynamic positron emission tomography (PET) imaging

Intervention Type: DRUG

Injection of hyperpolarized [1-13C]Pyruvate

Injection of one bolus of 0.43 ml/kg of approximately 250 mM hyperpolarized \[1-13C\]Pyruvate followed by magnetic resonance spectroscopy (MRS) / magnetic resonance spectroscopy imaging (MRSI). After a 5-30 min pause, injection of a second bolus of 0.43 ml/kg of approximately 250 mM hyperpolarized \[1-13C\]Pyruvate followed by MRS / MRSI.

Intervention Type: DRUG

PET/MR/MRS/MRSI scanning

Regional dynamic PET acquisition for up to 90 minutes following 18F-FDG injection is performed focused on a region-of-interest (ROI). Anatomical magnetic resonance imaging (MRI) is performed in the ROI, including diffusion weighted imaging (DWI) and contrast enhanced imaging (DCE). MRS/MRSI is performed following the injections of hyperpolarized \[1-13C\]Pyruvate.

Intervention Type: PROCEDURE

Other Intervention Names

18F-fluorodeoxyglucose; fluorodeoxyglucose-F-18; [18F]F-FDG

Eligibility Criteria

Inclusion Criteria

• Diagnosed with breast cancer, gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) grades G1, G2 or G3, lymphoma or sarcoma
• Measurable solid tumor of at least 1.5 cm
• Capable of understanding the patient information in Danish and giving full informed consent

Exclusion Criteria

• Pregnancy
• Breast-feeding
• Weighs above 140 kg and/or with abdominal circumference exceeding the gantry of the PET/MR coil (120 cm)
• History of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FDG or pyruvate
• Patients who are unable to lie in the MR scanner for up to 90 minutes
• Pace-maker
• Metallic implantations within the past 6 weeks
• Non-MR compatible implants
• Claustrophobia
• Participants who have not fasted for a minimum of 4 hours prior to the planned scan time

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Mathias Loft

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mathias Loft, MD

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Andreas Kjaer, MD

Role: STUDY_DIRECTOR

Rigshospitalet, Denmark

Locations

Rigshospitalet

Copenhagen, , Denmark

Countries

Denmark

Other Identifiers

AK_2021_HP

Identifier Type: -

Identifier Source: org_study_id