Fludeoxyglucose F 18 PET Imaging in Determining Protein and Gene Expression Signatures in Patients With Premalignant Polyps or Colon Cancer

Pilot Study of Ex-Vivo Molecular Polyp Imaging Using 18-F Fluorodeoxyglucose (FGD) Positron Emission Tomography (PET) in the Determination of Protein and Gene Expression Signatures of Premalignant Polyps

RATIONALE: Diagnostic imaging procedures, such as fludeoxyglucose F 18 PET, may be effective in detecting cancer or recurrence of cancer, or premalignant polyps.

PURPOSE: This clinical trial is studying fludeoxyglucose F 18-PET imaging to see how well it works in determining protein and gene expression signatures in patients with premalignant polyps or colon cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Neoplasm of Uncertain Malignant Potential
• Intervention / Treatment: Genetic: gene expression analysis; Genetic: protein expression analysis; Procedure: therapeutic conventional surgery; Other: immunoenzyme technique; Genetic: DNA methylation analysis; Procedure: biopsy; Genetic: reverse transcriptase-polymerase chain reaction; Other: diagnostic laboratory biomarker analysis; Radiation: fludeoxyglucose F 18; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Genetic: fluorescence in situ hybridization

Detailed Description

OBJECTIVES:

Primary

• To determine the feasibility of ex-vivo imaging of colon cancer and colon polyps using fludeoxyglucose F 18 positron emission tomography (FDG PET).
• To evaluate the differences in molecular and genetic profiles between FDG-positive polyps and FDG-negative polyps to suggest what gene mutations and abnormal mRNA and/or protein expressions may be required for FDG avidity ("signature" for FDG avidity).

Secondary

• To evaluate the differences in molecular and genetic profiles between FDG-positive polyps and FDG-positive cancers to suggest what gene mutations and abnormal mRNA and/or protein expressions may be required for cancer formation ("signature" for cancer).
• To evaluate the differences in molecular and genetic profiles between normal colonic mucosa, polyps, and cancer.
• To evaluate the differences and similarities in molecular and genetic profiles between FDG-positive cancers and polyps.

OUTLINE: Part I: Patients receive fludeoxyglucose F 18 (FDG) IV followed 45-60 minutes later by surgery to remove part or all of the colon. Tissue samples of the colon undergo positron emission tomography (PET) imaging.

Part II: Tissue samples are analyzed for glucose transporters proteins (Glut-1, 2, 3, 4, 5, 7) via IHC; presence of K-ras mutation (invariable mutant site on codon 12, 13) via PCR; 18q deletion via fluorescence in situ hybridization (FISH) or DCC IHC; MCT-1, Hex-1, Hex-2, and COX-2 expression levels via quantitative RT-PCR method or western blot; APC mutation via PCR- In Vitro Synthesized-Protein Assay or RT-PCR direct sequencing method; p53 mutation detection via immunochemistry, RT-PCR direct sequence methods, and western blot; methylation alteration of MGMT, CDKN2A, HLTF, MLH1, TIMP3, HIF1, BNIP3, and HRK via methylation detecting microchip; and specific gene methylations via methylation-specific PCR. Some tissue samples may be saved and banked for future studies.

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

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

MSK clinic

Description

Subject Inclusion Criteria:

• Patients eligible for entry into the study are those:
• Age 15 to 100
• Undergoing resection of a non-sarcomatous primary colon neoplasm who also has 2 or more adenomas each greater than or equal to 7-10mm in size which are anticipated to be removed with the colon specimen.
• It will be known from MSKCC or outside studies (barium enema, endoscopy, PET/CT, or CT colonography) that the patient has at least 2 proven adenomas 7-10 mm or greater and a primary colon neoplasm

Subject Exclusion Criteria:

• Insulin-dependent diabetics (as established by routine history and presurgical laboratory tests).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

resection of a non-sarcomatous primary colon neoplasm; The surgically removed colon will undergo ex-vivo imaging after examination in pathology. A PET scanner will be used to acquire a scan of the whole specimen.

Genetic: gene expression analysis; Genetic: protein expression analysis; Procedure: therapeutic conventional surgery; Other: immunoenzyme technique; Genetic: DNA methylation analysis; Procedure: biopsy; Genetic: reverse transcriptase-polymerase chain reaction; Other: diagnostic laboratory biomarker analysis; Radiation: fludeoxyglucose F 18; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Genetic: fluorescence in situ hybridization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Feasibility of ex-vivo imaging of colon cancer and colon polyps using fludeoxyglucose F 18 positron emission tomography (FDG PET)	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Differences in molecular and genetic profiles between FDG-positive polyps and FDG-negative polyps to suggest what gene mutations and abnormal mRNA and/or protein expressions may be required for FDG avidity ("signature" for FDG avidity)	2 years
Differences in molecular and genetic profiles between FDG-positive polyps and FDG-positive cancers to suggest what gene mutations and abnormal mRNA and/or protein expressions may be required for cancer formation ("signature" for cancer)	2 years
Differences in molecular and genetic profiles between normal colonic mucosa, polyps, and cancer	2 years
Differences and similarities in molecular and genetic profiles between FDG-positive cancers and polyps	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marc J. Gollub, MD, Memorial Sloan Kettering Cancer Center; Principal Investigator: Suresh Jhanwar, PhD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: October 25, 2007
• First Submitted That Met QC Criteria: October 25, 2007
• First Posted (Estimate): October 30, 2007

Study Record Updates

• Last Update Posted (Estimate): December 23, 2015
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: colon cancer; neoplasm of uncertain malignant potential
• Additional Relevant MeSH Terms: Neoplasms; Precancerous Conditions; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 07-114; P30CA008748 (U.S. NIH Grant/Contract); MSKCC-07114