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Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies.

ABSTRACT: PURPOSE:To determine if one venous blood sample can substitute full arterial sampling in quantitative modeling for multiple positron emission tomography (PET) radiotracers using simultaneous estimation of the input function (SIME). PROCEDURES:Participants underwent PET imaging with [11C]ABP688, [11C]CUMI-101, and [11C]DASB. Full arterial sampling and additional venous blood draws were performed for quantification with the arterial input function (AIF) and SIME using one arterial or venous (vSIME) sample. RESULTS:Venous and arterial metabolite-corrected plasma activities were within 6 % of each other at varying time points. vSIME- and AIF-derived outcome measures were in good agreement, with optimal sampling times of 12 min ([11C]ABP688), 90 min ([11C]CUMI-101), and 100 min ([11C]DASB). Simulation-based power analyses revealed that SIME required fewer subjects than the AIF method to achieve statistical power, with significant reductions for [11C]CUMI-101 and [11C]DASB with vSIME. Replication of previous findings and test-retest analyses bolstered the simulation analyses. CONCLUSIONS:We demonstrate the feasibility of AIF recovery using SIME with one venous sample for [11C]ABP688, [11C]CUMI-101, and [11C]DASB. This method simplifies PET acquisition while allowing for fully quantitative modeling, although some variability and bias are present with respect to AIF-based quantification, which may depend on the accuracy of the single venous blood measurement.

SUBMITTER: Bartlett EA

PROVIDER: S-EPMC6555699 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies.

Bartlett Elizabeth A EA Ananth Mala M Rossano Samantha S Zhang Mengru M Yang Jie J Lin Shu-Fei SF Nabulsi Nabeel N Huang Yiyun Y Zanderigo Francesca F Parsey Ramin V RV DeLorenzo Christine C

Molecular imaging and biology 20191001 5

<h4>Purpose</h4>To determine if one venous blood sample can substitute full arterial sampling in quantitative modeling for multiple positron emission tomography (PET) radiotracers using simultaneous estimation of the input function (SIME).<h4>Procedures</h4>Participants underwent PET imaging with [<sup>11</sup>C]ABP688, [<sup>11</sup>C]CUMI-101, and [<sup>11</sup>C]DASB. Full arterial sampling and additional venous blood draws were performed for quantification with the arterial input function (A ...[more]

PMID: 30535672

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies.

Publications

Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies.

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