Fifty-eighth annual meeting of the american association of physicists in medicine
SU-F-J-07: Evaluating the Adequacy of Biopsy Specimens for Genetic Signature Assessment by Measuring the Metabolic Activity in Specimens Obtained Under 18F-FDG PET/CT Guidance
Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity.
We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT guidance. The expected tumor cell concentration in biopsy specimens was evaluated from the amount of DNA needed (∼100 µg) and the number of pathology sections typically used for the analysis. The average 18F-FDG uptake per cell was measured by incubating KPC-4662 pancreatic tumor cells and HT-29 colorectal adenocarcinoma tumor cells in 18F-FDG containing solution (activity concentrations between 0.0122 and 1.51 MBq/mL and glucose concentrations of 3.1 and 1 g/L) for 1 to 1.75 hours and then measuring the activity of a known number of cells. Measurements of surrogate specimens obtained using 18G needle biopsies of gels containing these cells in expected concentrations (∼104 µL−1) were performed using an autoradiography CCD based device (up to 20 min exposure) and a scintillation well counter (∼1 min measurements) about 3 and 5 hours after the end of incubation respectively.
At start of autoradiography there were between 0.16 and 1.5 18F-FDG molecules/cell and between 1.14 and 5.43×107 18F-FDG molecules/mL. For the scintillation well counter, sample to minimum-detectable-count rate ratios were greater than 7 and the counting error was less than 25% for ≤80 s measurement times. Images of the samples were identifiable on the autoradiograph for ∼10 min and longer exposure times.
Scintillation well counter measurements and CCD based autoradiography have adequate sensitivity to detect the tumor burden needed for genetic profiling in 18G core needle biopsies.
Supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and by a sponsored research agreement with Biospace Lab S.A.