Molecular Imaging and Biology / PIK3CA Mutational Status Is Associated with High Glycolytic Activity in ER+/HER2 Early Invasive Breast Cancer : a Molecular Imaging Study Using [18F]FDG PET/CT

Purpose In PIK3CA mutant breast cancer, downstream hyperactivation of the PI3K/AKT/mTOR pathway may be associated with increased glycolysis of cancer cells. The purpose of this study was to investigate the functional association of PIK3CA mutational status and tumor glycolysis in invasive ER+/HER2 early breast cancer. Procedures This institutional review board-approved retrospective study included a dataset of 67 ER+/HER2 early breast cancer patients. All patients underwent 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography ([18F]FDG PET/CT) and clinico-pathologic assessments as part of a prospective study. For this retrospective analysis, pyrosequencing was used to detect PIK3CA mutations of exons 4, 7, 9, and 20. Tumor glucose metabolism was assessed semi-quantitatively with [18F]FDG PET/CT using maximum standardized uptake values (SUVmax). SUVmax values were corrected for the partial volume effect, and metabolic tumor volume was calculated using the volume of interest automated lesion growing function 2D tumor size, i.e., maximum tumor diameter was assessed on concurrent pre-treatment contrast-enhanced magnetic resonance imaging. Results PIK3CA mutations were present in 45 % of all tumors. Mutations were associated with a small tumor diameter (p < 0.01) and with low nuclear grade (p = 0.04). Glycolytic activity was positively associated with nuclear grade (p = 0.01), proliferation (p = 0.002), regional lymph node metastasis (p = 0.015), and metabolic tumor volume (p = 0.001) but not with tumor size/T-stage. In invasive ductal carcinomas, median SUVmax was increased in PIK3CA-mutated compared to wild-type tumors; however, this increase did not reach statistical significance (p = 0.05). Multivariate analysis of invasive ductal carcinomas revealed [18F]FDG uptake to be independently associated with PIK3CA status (p = 0.002) and nuclear tumor grade (p = 0.046). Size, volume, and regional nodal status had no influence on glycolytic activity. PIK3CA mutational status did not influence glycolytic metabolism in lobular carcinomas. Glycolytic activity and PIK3CA mutational status had no significant influence on recurrence-free survival or disease-specific survival. Conclusions In ER+/HER2 invasive ductal carcinomas of the breast, glucose uptake is independently associated with PIK3CA mutations. Initial data suggest that [18F]FDG uptake reflects complex genomic alterations and may have the potential to be used as candidate biomarker for monitoring therapeutic response and resistance mechanisms in emerging therapies that target the PI3K/AKT/mTOR pathway.(VLID)364366

Assessment of the kidney function parameters split function, mean transit time, and outflow efficiency using dynamic FDG-PET/MRI in healthy subjects

Abstract Background Traditionally, isotope nephrography is considered as the method of choice to assess kidney function parameters in nuclear medicine. We propose a novel approach to determine the split function (SF), mean transit time (MTT), and outflow efficiency (OE) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) dynamic positron emission tomography (PET). Materials and methods Healthy adult subjects underwent dynamic simultaneous FDG-PET and magnetic resonance imaging (PET/MRI). Time-activity curves (TACs) of total kidneys, renal cortices, and the aorta were prospectively obtained from dynamic PET series. MRI images were used for anatomical correlation. The same individuals were subjected to dynamic renal Technetium-99 m-mercaptoacetyltriglycine (MAG3) scintigraphy and TACs of kidneys; the perirenal background and the left ventricle were determined. SF was calculated on the basis of integrals over the TACs, MTT was determined from renal retention functions after deconvolution analysis, and OE was determined from MTT. Values obtained from PET series were compared with scintigraphic parameters, which served as the reference. Results Twenty-four subjects underwent both examinations. Total kidney SF, MTT, and OE as estimated by dynamic PET/MRI correlated to their reference values by r = 0.75, r = 0.74 and r = 0.81, respectively, with significant difference (p < 0.0001) between the means of MTT and OE. No correlations were found for cortex FDG values. Conclusions The study proofs the concept that SF, MTT, and OE can be estimated with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients receiving a routine PET/MRI scan, as kidney parameters can be estimated simultaneously to functional and morphological imaging with high accuracy

Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects

Abstract Background A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[18F]fluoro-d-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans. Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples. Results Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means. Conclusions The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications

Fully Automated, Semantic Segmentation of Whole-Body 18F-FDG PET/CT Images Based on Data-Centric Artificial Intelligence.

We introduce multiple-organ objective segmentation (MOOSE) software that generates subject-specific, multiorgan segmentation using data-centric artificial intelligence principles to facilitate high-throughput systemic investigations of the human body via whole-body PET imaging. Methods: Image data from 2 PET/CT systems were used in training MOOSE. For noncerebral structures, 50 whole-body CT images were used, 30 of which were acquired from healthy controls (14 men and 16 women), and 20 datasets were acquired from oncology patients (14 men and 6 women). Noncerebral tissues consisted of 13 abdominal organs, 20 bone segments, subcutaneous fat, visceral fat, psoas muscle, and skeletal muscle. An expert panel manually segmented all noncerebral structures except for subcutaneous fat, visceral fat, and skeletal muscle, which were semiautomatically segmented using thresholding. A majority-voting algorithm was used to generate a reference-standard segmentation. From the 50 CT datasets, 40 were used for training and 10 for testing. For cerebral structures, 34 18F-FDG PET/MRI brain image volumes were used from 10 healthy controls (5 men and 5 women imaged twice) and 14 nonlesional epilepsy patients (7 men and 7 women). Only 18F-FDG PET images were considered for training: 24 and 10 of 34 volumes were used for training and testing, respectively. The Dice score coefficient (DSC) was used as the primary metric, and the average symmetric surface distance as a secondary metric, to evaluate the automated segmentation performance. Results: An excellent overlap between the reference labels and MOOSE-derived organ segmentations was observed: 92% of noncerebral tissues showed DSCs of more than 0.90, whereas a few organs exhibited lower DSCs (e.g., adrenal glands [0.72], pancreas [0.85], and bladder [0.86]). The median DSCs of brain subregions derived from PET images were lower. Only 29% of the brain segments had a median DSC of more than 0.90, whereas segmentation of 60% of regions yielded a median DSC of 0.80-0.89. The results of the average symmetric surface distance analysis demonstrated that the average distance between the reference standard and the automatically segmented tissue surfaces (organs, bones, and brain regions) lies within the size of image voxels (2 mm). Conclusion: The proposed segmentation pipeline allows automatic segmentation of 120 unique tissues from whole-body 18F-FDG PET/CT images with high accuracy

Additional file 1: of Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects

FDG TAC analysis. (DOCX 11 kb