A Pilot Study of 18F-FLT in Pediatric Patients With Central Nervous System (CNS) Tumors (FLT)

A Pilot, Non-Therapeutic NeuroImaging Study of 18F-FLT in Pediatric Patients With Newly Diagnosed Central Nervous System Tumors

In spite of numerous advances in neuroimaging techniques, the diagnosis of pediatric brain tumors relies on the pathologic evaluation of material obtained at the time of the initial operation. While 18F-FDG-positron emission tomography (PET) helps identify higher-grade lesions due to their increased glucose metabolism, the high tracer uptake of the normal adjacent brains makes this modality of limited value. Fluorine-18 fluorothymidine (FLT) is a new imaging agent that has two significant advantages in the imaging of CNS tumors. First, this agent detects cellular proliferation directly, and second, the normal brain does not take up the agent, making a positive area(s) easy to identify. Before embarking on a large pediatric disease stratified assessment of FLT imaging in pediatric neurooncology patients, the investigators are proposing a limited patient pilot study to evaluate the biodistribution, dosimetry and specificity of this compound when compared to immunohistochemical assessment of mitotic activity in newly diagnosed patients undergoing surgical resection.

Study Overview

• Status: Terminated
• Conditions: Tumors of the Central Nervous System
• Intervention / Treatment: Drug: 18F-FLT; Radiation: PET Imaging

Detailed Description

Patients will undergo standard pre-diagnostic imaging of the sites of disease using standard MRI techniques. If disease is suspected in both the brain and spine, then both imaging modalities should be obtained. This imaging should be obtained no more than 21 days before surgical resection. As close as possible to the completion of the MRI scans, patients will undergo 18F-FLT imaging using a single administration of tracer, and PET image acquisition at four different time points (baseline, 1 hr post injection, 2 hrs post injection and 4-6 hours post injection). A whole body PET scan (top of the head to mid thigh) will be performed immediately after injection (PET acquisition #1). These data will be acquired with a 2 minute emission and a 2 minute transmission scan at each bed position. Following this acquisition, the subject will empty his or her bladder. At 45 minutes post-injection, a brain and/or spine (body) PET scan will be acquired with a 10 min emission scan and a 5 min transmission scan (PET acquisition #2). This scan will include all areas of suspected tumor (brain, spine, or brain and spine). Following PET acquisition #2, a whole body PET scan will be acquired according to the same protocol as above (PET acquisition #3). If possible, a final whole body scan will be acquired 4-6 h post-injection (PET acquisition #4). All PET acquisitions will be acquired in 3D mode and reconstructed with the FORE re-binned OSEM algorithm with measured attenuation correction. Blood samples will be obtained at the completion of each whole body scan. Patients will receive the dose of 18F-FLT through a fresh intravenous catheter as per standard PET procedures. Patients will then undergo maximal surgical resection. Pieces from different areas of the tumor will be marked for correlation to imaging studies when possible. Tumor samples will undergo standard immunohistochemical analysis for cellular activation including mitotic index and MIB-1 proliferation staining.

Serial blood draws will also be obtained at four different time points (baseline, 1 hr post injection, 2 hrs post injection, and 4-6 hours post injection) to evaluate clearance of 18F-FLT from the blood.

For the biodistribution, the 3D regions of interest (ROIs) will be drawn about each major organ that is identified on the whole body scans. This will be performed on each of the whole body scans and a time activity curve will be generated. The residence time for each organ will be determined. The blood data will be pipetted and counted for estimates of activity in the blood and bone marrow. For the brain and/or spine images, the PET data will be registered to the subjects' MRI. The PET scan will be graded on a subjective 4-point scale. 3D ROIs will be drawn around the tumor. In addition, an analogous ROI will be drawn in normal brain background and about the whole brain for comparison. For the tumor, tumor-to-background, tumor-to-whole brain ratios will be determined. In addition, standard uptake values (SUVs) will be determined for the tumor and background.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients with newly diagnosed central nervous system tumors undergoing planned surgical resection within 21 days.
• Patients should be < 21 years of age at the time of diagnosis.
• Patients should be capable of achieving imaging without the need for sedation or anesthesia.
• Karnofsky Performance Status ≥ 50. For infants, the Lansky play scale ≥ 50% can be substituted.
• Patients must not be pregnant or nursing.
• Signed Informed Consent.
• Patients receiving steroids and/or anti-seizure medications are eligible for this study.

Exclusion Criteria:

• Prior radiation therapy and/or chemotherapy are not permitted.
• Active infection
• Pregnancy or breast feeding
• Serious concurrent medical illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 18F-FLT; All subjects will receive 18F-FLT prior to PET imaging.	Drug: 18F-FLT; Patients will receive a dose of 18F-FLT through a fresh intravenous catheter as per standard PET procedures. Dosing will be based on age.; Other Names: 18F]-Fluorothymidine; Radiation: PET Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the distribution, localization and kinetics of localization of 18F-FLT in pediatric patients with central nervous system tumors	Assessed shortly after subjects undergo neuroimaging

Secondary Outcome Measures

Outcome Measure	Time Frame
To correlate the activity of administering 18F-FLT in newly diagnosed pediatric brain tumor patients to standard immunohistochemical markers of cellular activation and MRI imaging	Assessed shortly after subjects undergo neuroimaging

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Boston Children's Hospital
• Investigators: Principal Investigator: Mark Kieran, MD, Dana-Farber Cancer Institute/Children's Hospital Boston

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimate): March 12, 2008

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: PET; FLT; diagnosed; CNS tumors; 18F-FLT; Newly
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Anti-Infective Agents; Antiviral Agents; Alovudine
• Other Study ID Numbers: 05-303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes