Katie Moses

University of Colorado Health

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Michael Silosky

University of Colorado Anschutz Medical Campus

Bennett B. Chin

University of Colorado Anschutz Medical Campus

Amber Pierret

University of Colorado Hospital

Ramesh Karki

Tribhuvan University

Cooperative Institutions

University of Colorado Denver

University of Colorado Anschutz Medical Campus

The University of Texas MD Anderson Cancer Center

The University of Texas Health Science Center at Houston

Tribhuvan University

Swinburne University of Technology

University of Turku

Colorado State University

University of Colorado Hospital

University of Colorado Health

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68Ga DOTATATE tumor uptake: Pheochromocytomas and paragangliomas versus pancreatic and small bowel gastroenteropancreatic neuroendocrine tumors

Journal of Nuclear Medicine (2020)

Katie Moses Michael Silosky Ramesh Karki Bennett B. Chin

3033 Objectives: Pheochromocytomas and paragangliomas (PPG) are rare neuroendocrine tumors which may be amenable to surgical excision or systemic therapy. Metastatic or unresectable PPG may be imaged and treated with targeted neuroendocrine transporter 1 (NET1) radionuclide therapy using meta-iodobenzylguanidine (MIBG). MIBG tumor imaging and therapy, however, may be suboptimal to due low NET1 expression or tumor heterogeneity. An alternative theranostic target is the somatostatin receptor 2 (SSR2) via DOTATATE. If DOTATATE tumor uptake in PPG is high, DOTATATE could be tested as an additional or complimentary theranostic strategy. The purpose of this study is to compare 68Ga DOTATATE uptake in PPG compared to the established indications of small bowel and pancreatic neuroendocrine (GEPNET) tumors. Methods: We retrospectively reviewed 50 consecutive patients referred for 68Ga DOTATATE PET/ CT imaging. A single outlier PPG subject with extremely high tumor uptake (SUVmax > 300) was excluded. Of the remaining subjects with identifiable tumor, we quantified the tumor uptake and target to background ratios (T/B) in subjects with PPG (n=5 subjects; 14 lesions) compared to small bowel neuroendocrine and pancreatic (GEPNET) tumors (n=20 subjects; 44 lesions). Tumors were contoured using a semi-automated program based on a modified PERCIST criteria. SUVmax and SUVmean were measured and tumor/background was calculated as the ratio of SUVmax in the tumor to SUVmean in the aortic blood pool. Mean values and standard deviations were calculated for SUVmax, SUVmean, and T/B. Results: High tumor uptake in PPG (SUVmax = 36.7 + 21.4) was comparable to GEPNETS (SUVmax = 37.8 + 23.5), and not found to be significantly different via t-test (p=0.90). High T/B in PPG (T/B = 40.2 + 28.6) were also comparable to GEPNET (T/B = 42.2 + 41.1), and again not significantly different (p=0.90). The PPG tumor uptake ranged from 6.3 to 66.7. Using a modified PERCIST threshold to define the tumor boundaries, the average SUVmean of the PPG tumors was 8.4 + 4.2. Conclusions: PPG may show high tumor uptake and T/B in 68Ga DOTATATE PET / CT imaging. This data supports further investigations of DOTATATE as an alternative or complimentary theranostic for imaging and therapy of metastatic or unresectable PPG.

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Advanced PET imaging simultaneously improves image noise and patient throughput in 68Ga DOTATATE scans

Journal of Nuclear Medicine (2021)

Katie Moses Amber Pierret Michael Silosky Bennett B. Chin

189 Objectives: The benefits of both advanced digital detectors and larger field of view, available on modern PET scanners, have been well characterized in the scientific literature. However, the clinical benefits to patient imaging from the radiologists’ perspective and from the technologists’ perspective have not been well quantified. Generally, the higher sensitivity of modern devices has allowed PET imaging facilities to consider changes to imaging protocols including shorter bed durations. This is often handled qualitatively with physicians noting that the image quality is better on new devices, however, this is a relatively subjective assessment. Recently, our facility has replaced a smaller field of view analog PET/CT scanner with a modern digital device with an extended axial field of view. The purpose of this study is to quantify improvements in image quality as measured by image noise as well as quantify improvement in patient throughput as measured by total scan time. Methods: To quantitatively assess differences in image quality between older and modern devices, regions of interest (ROI) were drawn in the blood pool (aorta) and liver for 20 68Ga DOTATATE patients. The first 10 studies were acquired on an older Discovery STE (General Electric, Waukesha WI) with an approximately 15 cm axial extent and the second 10 from the new Discovery MI PET / CT (General Electric, Waukesha WI) with an approximately 25 cm axial extent. All scans were performed with 5 minutes per bed, iterative reconstruction, and used 5 mm post reconstruction gaussian smoothing. Care was taken to ensure the ROIs avoided tissue boundaries and areas of heterogeneous uptake. SUVmean and standard deviation were measured in each region and the coefficient of variation within each region was calculated. To determine if differences in these parameters were statistically significant, a two tailed t-test was performed. To assess changes in patient throughput, the number of bed positions was tracked for each patient and used to calculate total scan time. Additionally, the time that the patient entered and exited the PET/CT scanner room was tracked for the 10 Discovery MI patients to relate differences in scan time, to the total time the patient occupies the imaging suite. Results: The average SUVmean in the liver was 5.21 ± 1.38 and 6.20 ± 2.67 for the Discovery STE and Discovery MI, respectively. The difference was not statistically significant (p = 0.30). The average standard deviation in the liver was 1.03 ± 0.38 and 0.30 ± 0.11 for the Discovery STE and Discovery MI, respectively. This difference was statistically significant (p < 0.001). Similar findings were observed in the blood pool with the average values of SUVmean of 1.00 ± 0.29 and 1.11 ± 0.37 (not significantly different, p = 0.38) and average standard deviations of 0.23 ± 0.07 and 0.13 ± 0.04 (significantly different, p < 0.01), for Discovery STE and Discovery MI PET / CT, respectively. Regarding throughput, patients imaged on the Discovery STE required either 6 or 7 bed positions (average = 6.64) resulting in an average imaging time of 33.2 minutes. Patients imaged on the Discovery MI all required 5 bed positions resulting in a 25-minute imaging time. Tracking the total room time for Discovery MI patients indicated that the amount of time spent in the room, not during scanning was on average 9.5 minutes. Consequently, use of the new scanner reduced total room time on average from 42.7 minutes per exam to 34.5 minutes per exam. Conclusions: Modern digital PET / CT system with a large field of view can simultaneously achieve reduced total clinical imaging time and improvement in image quality while maintaining the same time per bed position. Quantification of imaging times and imaging metrics can support the rational design of clinical protocols which optimize the acquisition parameters and simultaneously improve image quality.

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Effects of image matrix on quantitative metrics in 68Ga DOTATATE studies: Changes in SUV and signal-to-noise ratio in modern digital PET detectors

Journal of Nuclear Medicine (2021)

Amber Pierret Katie Moses Michael Silosky Bennett B. Chin

3040 Objectives: Modern digital PET detectors can dramatically improve PET sensitivity and spatial resolution. As novel theranostic agents for prostate cancer, fibroblast activating protein inhibitor, and other targets continue towards clinical development, an opportunity arises for improving patient care through improving small lesion detectability. With increasing digital PET sensitivity and spatial resolution, improving small lesion detectability by improving acquisition parameters such as image matrix size is now feasible. The purpose of this study is to quantify the effect of matrix size in 68Ga DOTATATE PET scans on SUV and signal-to-noise ratio (SNR) using a modern digital PET system. Methods: Ten 68Ga DOTATATE patients were imaged using a Discovery MI (General Electric, Waukesha WI) PET/CT system. All scans were performed with 5 minutes per bed position using the QClear reconstruction tool with B = 400. Images were reconstructed at the following matrix sizes: 192 x 192, 256 x 256, and 384 x 384 correlating to 3.6, 2.7 and 1.8 mm. To evaluate the effects of matrix size on lesion SUV and SNR, regions of interest (ROI) were created over known tumors (n=66) using PET edge plus (MIM v7.0) by an experienced nuclear medicine radiologist. These ROIs were then superimposed on all reconstructed image sets, and SUVmax and SUVmean were recorded for each tumor. To evaluate SNR, ROIs were placed in the blood pool (aorta) and liver to measure background SUVmean and standard deviation for hepatic and extrahepatic tumors. Care was taken to ensure the ROIs avoided tissue boundaries and areas of heterogeneous uptake. SNR for each tumor was calculated as the difference in SUVmean in the tumor to SUVmean in the background, divided by the standard deviation of the background. Additionally, tumors were divided into two groups: small tumors (< 1.0 cm diameter, n = 36) and large tumors (≥ 1.0 cm diameter, n = 30). To determine if differences in uptake metrics or SNR were statistically significant, a series of paired t-tests were performed. Results: For both small and large lesions, increasing the matrix size led to a small reduction in SUVmax. For large lesions, the average SUVmax was 44.8, 44.0, and 42.8 for the 192, 256, and 384 matrix sizes, respectively. For small lesions, the average SUVmax was and 17.6, 17.2, and 16.9 for the 192, 256, and 384 matrix sizes, respectively. These differences, however, were not found to be statistically significant. For SUVmean, increasing the matrix size from 192 to either 256 or 384 lead to a very small but statistically significant increase (p<0.05). SUVmean differences between the 256 and 384 matrix sizes were not significantly different. The SNR, however, showed significant differences between matrix sizes. For large lesions, increasing matrix size led to a statistically significant increases in average SNR values of 124.3, 128.6, and 137.2 for 192, 256, and 384 matrix sizes. For small lesions, increasing matrix size led to statistically significant increases in the SNR values of 82.7, 89.2, and 91.7 for 192, 256, and 384 matrix sizes, respectively. Conclusions: For clinically acquired 68Ga DOTATATE PET, SNR increases as matrix size is increased. SUVmean showed only small changes, and SUVmax was not significantly affected by matrix size. Changing matrix size suggests a potential to influence lesion detectability, but requires further investigation.

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