Purpose: Genomic profiling of biopsied tissue is the basis for precision cancer therapy. However, biopsied materials may not contain sufficient amounts of tumor deoxyribonucleonic acid needed for the analysis. We propose a method to determine the adequacy of specimens for performing genomic profiling by quantifying their metabolic activity.
Methods: We estimated the average density of tumor cells in biopsy specimens needed to successfully perform genomic analysis following the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) protocol from the minimum amount of deoxyribonucleonic acid needed and the volume of tissue typically used for analysis. The average F-FDG uptake per cell was assessed by incubating HT-29 adenocarcinoma tumor cells in F-FDG containing solution and then measuring their activity with a scintillation well counter. Consequently, we evaluated the response of two devices around the minimum expected activities which would indicate genomic profiling adequacy of biopsy specimens obtained under F-FDG PET/CT guidance. Surrogate samples obtained using 18G core needle biopsies of gels containing either F-FDG-loaded cells in the expected concentrations or the corresponding activity were measured using autoradiography and a scintillation well counter. Autoradiography was performed using a CCD-based device with real-time image display as well as with digital autoradiography imaging plates following a 30-min off-line protocol for specimen activity determination against previously established calibration.
Results: Cell incubation experiments and estimates obtained from quantitative autoradiography of biopsy specimens (QABS) indicate that specimens acquired under F-FDG PET/CT guidance that contained the minimum amount of cells needed for genomic profiling would have an average activity concentration in the range of about 3 to about 9 kBq/mL. When exposed to specimens with similar activity concentration, both a CCD-based autoradiography device and a scintillation well counter produced signals with sufficient signal-to-background ratio for specimen genomic adequacy identification in less than 10 min, which is short enough to allow procedure guidance.
Conclusion: Scintillation well counter measurements and CCD-based autoradiography have adequate sensitivity to detect the tumor burden needed for genomic profiling during F-FDG PET/CT-guided 18G core needle biopsies of liver adenocarcinoma metastases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948146 | PMC |
http://dx.doi.org/10.1002/mp.12836 | DOI Listing |
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