Methionine and PBR28-PET (Peripheral Benzodiazepine Receptors) in Brain Metastases Following Radiosurgery

Studies of Methionine-PET and PBR28-PET in Brain Metastases to Differentiate Tumor Recurrence and Radiation Necrosis Following Stereotactic Radiosurgery

The goal of this protocol is to evaluate the potential of PET imaging of amino acid transport and microglial activation to improve the differentiation of tumor recurrence and radiation necrosis in patients with brain metastases after treatment with stereotactic radiosurgery (SRS) who have re-growing lesions. These state-of-the-art imaging tools will be used in combination with standard magnetic resonance imaging (MRI), MR spectroscopy (MRS) and FDG-PET (fluorodeoxyglucose).

Study Overview

• Status: Terminated
• Conditions: Brain Metastasis
• Intervention / Treatment: Procedure: Standard of Care FDG-PET Imaging

Detailed Description

The investigators hypothesize that by using two different PET tracers, one sensitive to tumor metabolic activity, and one sensitive to inflammatory processes, investigators can separately identify metabolically active tumor from radiation necrosis related inflammation. This can be accomplished with quantitative assessments of tracer uptake using kinetic modeling techniques, as well as by high-resolution imaging to assess the distribution of tracer uptake in the tumor region. All participants in the study will have the receive the same diagnostic tests.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who received SRS for melanoma or NSCLC brain metastases with regrowing lesions who are candidates for surgical intervention (biopsy or excision) at the Smilow Cancer Center or are candidates for monitoring by serial imaging will be screened for eligibility and offered enrollment

Description

Inclusion Criteria:

• Patients over 18 years with brain metastases from melanoma or non-small cell lung cancer
• Patients must have had SRS and regrowth in at least one lesion > 0.5 cm in greatest dimension and fall into one of two categories: a) patient is deemed clinically appropriate for surgical intervention (biopsy or craniotomy) OR b) patient is asymptomatic and has a life expectancy of > 6 months so that serial follow-up imaging is appropriate
• Willingness to participate in imaging studies
• Able to give informed consent

Exclusion Criteria:

• Subjects with history of prior radiation exposure for research purposes within the past year, such that participation in this study would place them over the FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year.
• Subjects who are pregnant or currently breastfeeding
• Women of child-bearing age who are sexually active, unless they agree to two forms of contraception, and have a negative urine pregnancy test at screening and on the days of the PET imaging
• Patients unable to undergo MRI with gadolinium-based contrast for standard clinical reasons which include:
• Cardiac pacemaker, aneurysm clip, cochlear implants, Intra Uterine Device (IUD), shrapnel, neurostimulators, defibrillator, artificial heart valve, or history of metal fragments in eyes.
• Pregnancy
• Body size too large for closed MRI
• Known hepatic fibrosis.
• Claustrophobia
• Contraindication to MR contrast agents: eGFR (epidermal growth factor receptor) < 30 by the Cockcroft- Gault formula if > 60 years old or with chronic renal disease
• Anaphylactic allergy to gadolinium

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Melanoma Brain Metastases; Stage 4 cancer patient population with melanoma with brain metastases previously treated with SRS	Procedure: Standard of Care FDG-PET Imaging; [11C]Methionine [11]. This natural amino acid, and its various fluorinated derivatives, has been widely used in brain tumor studies due to a) high tumor-to-normal brain contrast, and b) its sensitivity to biological functions including amino acid transport and utilization. [11C]PBR28 [12]. This ligand is one of a series of second-generation tracers that bind to TSPO (translocator protein), a protein that is upregulated in activated microglia.; Other Names: DWI, MRPerfusion, MRSpectroscopy and FDG-PET
Lung Cancer Brain Metastases; Stage 4 cancer patient population with non-small cell lung cancer with brain metastases previously treated with SRS	Procedure: Standard of Care FDG-PET Imaging; [11C]Methionine [11]. This natural amino acid, and its various fluorinated derivatives, has been widely used in brain tumor studies due to a) high tumor-to-normal brain contrast, and b) its sensitivity to biological functions including amino acid transport and utilization. [11C]PBR28 [12]. This ligand is one of a series of second-generation tracers that bind to TSPO (translocator protein), a protein that is upregulated in activated microglia.; Other Names: DWI, MRPerfusion, MRSpectroscopy and FDG-PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Regrowing Tumor Rate from Radiation Effect	6 months

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Veronica Chiang, MD, Yale University

Publications and helpful links

General Publications

• Tran TT, Gallezot JD, Jilaveanu LB, Zito C, Turcu G, Lim K, Nabulsi N, Huang H, Huttner A, Kluger HM, Chiang VL, Carson R. [11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis. Mol Imaging. 2020 Jan-Dec;19:1536012120968669. doi: 10.1177/1536012120968669.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): June 27, 2017
• Study Completion (Actual): June 27, 2017

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 4, 2015

Study Record Updates

• Last Update Posted (Actual): May 28, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: regrowth; radiosurgery; radiation necrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 1401013294

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No