Importance To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant. Objective To evaluate the complete response rate as assessed by 18 F-fluorodeoxyglucose–positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma. Design, Setting, and Participants A single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT. Interventions Two cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment. Main Outcomes and Measures The primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety. Results Forty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting. Conclusions and Relevance Results suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant. Trial Registration ClinicalTrials.gov Identifier: NCT03077828

Key Points • One hundred percent of patients remain alive without relapse following sequential pembrolizumab and AVD after nearly 3 years of follow-up.• PD-1 pathway correlatives were not associated with the depth of response to PD-1 blockade.

173 Objectives: Attenuation correction (AC) is necessary for data quantification in PET imaging. PET reconstructions without AC appear to show areas of low attenuation (patient surface and lungs) as having increased uptake. Traditional methods of generating a transmission-based AC map (µ-map) are unavailable with PET/MR imaging. Instead, MR imaging sequences (DIXON) are utilized to generate the required µ-map. Previous experiments demonstrated the creation of an incomplete µ-map if only the breast coils were utilized (per clinical diagnostic breast MR protocol). A complete µ-map was generated when an additional body matrix coil was placed on the subject’s back. But, the additional coil limits the size of the subject that can be imaged due MR bore clearance issues. Siemens mMR scientists proposed and modified the DIXON based MRAC sequence (permit multiple averages) to allow for creation of complete µ-maps utilizing only the internal body coil. When first testing this solution in 2019, a complete µ-map was generated where the water and fat were flipped in the DIXON sequences producing inaccurate µ-maps and reduced Standardize Uptake Values (SUV). The aim of this project was to validate the creation and application of µ-maps generated with only the internal body coil in breast PET/MR imaging using new MR considerations. Methods: A volunteer was imaged utilizing DIXON sequences with two different coil configurations, the breast plus body matrix coil (the source of truth) and the internal body coil only. Two different types of breast tissue were evaluated this year, one as water (saline) and a second as fat (vegetable oil). To simulate lesions in a patient, three conical 1.5 mL vials containing a clinically relevant concentration of F18-FDG were placed in the mediastinal region of the right breast and in the central regions of both the right and left breasts. SUVs were obtained from regions of interest drawn around all three simulated lesions in both types of breast tissue. These values were compared for each generated µ-map and PET reconstruction - breast and body matrix coils (complete) and internal body coil (complete). Results: Please see Table 1. Conclusions: The results revealed similar SUVmax measurements between the breast and body matrix coils and the internal body coil with a variance of less than 5% regardless of the type of simulated breast tissue. These results indicate that µ-maps created with the internal body coil are a viable alternative to those generated with the breast and body matrix coils. These results should be further assessed and verified with patient imaging rather than simulated breast tissue.

175 Objectives: Spatial resolution testing of PET scanners, per the National Electric Manufacturers Association (NEMA) protocol, is performed using a very specific method. A 1 mm or smaller point source is imaged in air (with no attenuation or scatter) and reconstructed by filtered back projection (FBP) in a sub-clinical pixel size. The point source is located and acquired in specified locations in the PET field of view (FOV) utilizing a vendor provided application. Resolution assessment is performed by the same application, providing full width half max (FWHM) measurements in millimeters (mm) for each location. The aim of this project was to assess PET spatial resolution in a more clinically relevant method, utilizing clinical reconstruction methods and corrections (3D iterative reconstruction, attenuation, and scatter). Methods: A phantom study was performed to assess system resolution in a more clinically relevant manner utilizing typical clinical reconstruction methods on a Siemens Biograph PET-MR. A 22Na, 0.25 mm point source was first imaged in air, per the NEMA protocol, and reconstructed with FBP as well as with the system’s enhanced reconstruction algorithms. The point source was placed approximately 6 cm horizontally from the center of the field of view (FOV) and imaged for two million counts. The result of the measurement was then compared with the vendor provided analysis application. To assess the system spatial resolution in more clinical-like conditions, the 22Na point source was glued to the largest (37 mm) bulb of a NEMA Image Quality PET phantom. When imaged, this placed the source in approximately the same location as the measurement in air. The phantom was filled with water and imaged for two million counts. This data set was reconstructed with a 3D iterative algorithm using typical clinical parameters - 172x172 matrix (4.2 mm pixel, 3 iterations, 21 subsets, 3 mm Gaussian smoothing filter). Additional reconstructions were performed for comparison and potential application in clinical imaging. Results: Data acquired with and without the reconstructions were analyzed and FWHM values were calculated which are shown in Table 1. This experiment’s NEMA protocol resolution of 3.9 mm, 3.7 mm (x, y respectively) FWHM matches the results of the vendor provided application, demonstrating the validity of the analysis technique. Utilizing the enhanced techniques of 3D iterative reconstruction and full corrections dramatically improves resolution to 1.87 mm and 1.80 mm FWHM. As expected, FWHM increases when the point source is imaged in the phantom (3.08 mm, 3.04 mm). Decreasing the matrix size to the clinically utilized 172x172 (4.17 mm pixel) increases the FWHM to 4.66 mm and 4.64 mm. Increasing the matrix size to 256x256 (2.8 mm pixel) only marginally improves the FWHM to 4.13 mm and 4.58 mm. Conclusions: Although important, there are other aspects of PET imaging beyond spatial resolution (image contrast, image quality) to be assessed. In the absence of a more complete assessment of diagnostic image quality, further experiment of image quality should be performed before attempting to utilize increased matrix sizes to improve spatial resolution.

172 Objectives: Using smaller radiopharmaceutical doses for positron emission tomography (PET) imaging would be beneficial in lowering the radiation exposure to patients. However, reducing the given dose could impact the diagnostic quality of the images produced. Therefore, computer software reconstructions can be used to create images that simulate having given reduced radiopharmaceutical PET doses. The purpose of this study was to create PET images that simulate decreased injected doses to determine the effect on image quality and clinical confidence. Methods: Seventeen patients with recent 18F-FDG PET/CT scans were chosen to include in this study. These patients had varying amounts of disease. The patients also ranged in body mass index (BMI) from healthy, overweight, and obese. The patients’ PET data were first reconstructed in the standard manner to create images with 100% of the original dose. The data sets were then reconstructed to simulate having 75% and 50% of the original dose, creating 51 reconstructions in total. Each reconstruction was cleared of patient identifying information and randomly labeled as RD_01, RD_02, etc. The reconstructions were then reviewed by two expert readers. The radiologists scored the reconstructions using a 1 to 5 scale based on general image quality and basic clinical confidence. The scores were then grouped and averaged based on BMI ranges for each dose amount. Results: The overall scores of each BMI group for each reconstruction dose amount are shown in Table 1. The percent decreases from 100% of the dose to 75% and 50% doses for the average scores of each BMI range are shown in Table 2. Conclusions: As anticipated, reducing the simulated dose reduced both scored image quality and clinical confidence, with the largest decrease observed in image quality at the 50% dose level across all BMIs (11.8%). Scores for the 75% dose in the healthy and overweight BMI groups showed only a small reduction in clinical confidence (2.0%), indicating the potential for reducing the injected dose for these populations. The increased score in image quality at 75% of the dose for the overweight BMI group (-4.2%) skews the result of the overall decrease in image quality (1.9%). However, the small reduction in image quality at the 75% dose for the healthy BMI group demonstrates the potential for a decreased injected dose in this population. Additional readers and a larger sample of exams that includes a variety of disease burdens will be needed to refine and clarify these findings before a reduction of clinical 18F-FDG doses can occur.

3057 Objectives: 99mTc-macroaggregated albumin (MAA) is a liquid suspension of technetium-99m labeled to human aggregated particles. These radiolabeled MAA particles will settle when dispensed in syringes secondary to gravity. The purpose of this study was to determine the best dispensing configuration of these unit doses to optimize the net final dose activity administered to the patient. Methods: Forty 99mTc-MAA doses were dispensed in 3cc syringes and calibrated as 3 mCi, six hours post dispensing. The final volume of the MAA unit doses were standardized to 1.0 ml using sterile 0.9% sodium chloride. Six hours was chosen as the amount of time to simulate delivery and distribution to an off-site facility taking into consideration transportation and actual patient schedules. Of the 40 doses, 20 doses were drawn and dispensed with regular needles and the other 20 were capped with luer locks. After six hours, the doses were assayed, and the time and activity was recorded. Ten doses from each configuration were inverted and tapped twice (agitation) prior to injecting into an evacuated vial to simulate a typical patient injection. The other ten from each configuration were injected into the vial without any inversion and agitation. The residual of each syringe, needle and luer lock were assayed separately and recorded. Results: Data from the 40 99mTc-MAA unit doses were analyzed with the results summarized in Table 1. Conclusions: The results showed that there was a greater than 60% reduction in residual activity when the syringes were inverted and agitated prior to administration regardless of the configuration of the syringes. The dispensing configuration with the lowest average residual activity and variance was that which included a needle with inversion and agitation.

The Nuclear Medicine Global Initiative was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in 2 articles. For its second project the Nuclear Medicine Global Initiative chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals, and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals used in each country, and sources of supply, was evaluated. Responses highlighted problems in access, particularly due to the reliance on a sole provider, regulatory issues, and reimbursement, as well as issues of facilities and workforce, particularly in low- and middle-income countries. Conclusion: Strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the coronavirus disease 2019 outbreak, renewed focus on ensuring a reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.

3023 Objectives: Lu-177 Lutathera® therapy was approved by the FDA in 2018 to treat unresectable or metastatic neuroendocrine tumors. Currently, Lu-177-PSMA-617 is in phase III of clinical evaluation for metastatic castration resistant prostate cancer. Depending on the treatment plan, patients receive multiple Lu-177 treatments over a period of time and can be in the department for up to six hours for each treatment. Lu-177 emits both beta and gamma radiation, presenting several radiation safety concerns. The purpose of the evaluation was to determine radiation safety precautions for the infusion of Lu-177 therapies in the outpatient hospital setting. Methods: Lu-177 research and clinical therapies have been administered for approximately 18 months in our newly designed therapy suite. During this time the Radiation Safety department has been able to determine an effective approach for performing Lu-177 therapies in the outpatient setting to minimize contamination and reduce exposure to the care team. With over 200 Lu-177 therapies administered in our new therapy suite over the past 18 months, the Radiation Safety Department was able to determine an effective method for preparing the therapy room and bathroom to minimize contamination on permanent surfaces. Different absorbent material and toilet coverings were evaluated to determine which worked best at absorbing and preventing the spread of contamination in our facility. Surveys were initiated at the end of each treatment to measure potential contamination. The surveys were performed using a Ludlum 14C survey meter with pancake probe and by collecting multiple wipe samples to verify removable contamination was not present. The wipe samples were analyzed using a Packard Cobra II Auto-Gamma Counter. Syringe shield evaluation for Lu-177 was conducted using two different commercially available syringe shields. The shielding evaluation was performed by measuring the radiation dose, using thermoluminescent dosimeters (TLD), for two unit doses of Lu-177-PSMA-617 with activities of 166 mCi and 205 mCi. Two TLDs were placed on each unshielded syringe and exposed for 15 minutes and removed. Each unit dose was placed in a Biodex Beta Syringe Shield and a Pro-Tec III Syringe Shield with 2 TLDs positioned on the outside of each shield for 15 minutes. One TLD was used as a control. The TLDs were sent to Landauer Inc. for measurement. The results were multiplied by four to determine the dose per hour. Results: Versi-Dry® lab soaker with a waterproof backing provided ample absorbency for covering the bathroom floor and the floor around the injection area of the therapy room for minor spills and small bladder accidents. Disposable chux pads worked well at absorbing fluids around the floor of the toilet and the walls. The toilet seat was covered with plastic wrapping, to minimize the contamination of the seat. The average radiation dose rate from the unshielded syringes for Lu-177-PSMA-617 with an activity of 166 mCi and 205 mCi were 18160 mrem/hr and 22700 mrem/hr, respectively. The radiation dose rate from the 166 mCi and the 205 mCi doses in the Biodex Beta Syringe Shield averaged 520 mrem/hr and 560 mrem/hr, respectively. The radiation dose rate from the 166 mCi and the 205 mCi doses in the Pro-Tec III Syringe shield averaged 720 mrem/hr and 1040 mrem/hr, respectively. Conclusions: Effective prepping of the therapy room and bathroom will ensure easy cleanup and minimal decontamination efforts from the Radiation Safety staff. The Biodex Beta Syringe Shield is more effective at attenuating radiation than the Pro-Tec III Syringe Shield for Lu-177 therapy administrations.

3071 Objectives: During Positron Emission Tomography (PET) imaging, respiratory motion in the lungs can occur and cause lesions to appear blurred. The blurring of a lesion in PET imaging may influence the Standard Uptake Value (SUV) measurement and it could be reduced. With the recent installation of Siemens Biograph Vision and software updates we now have the capability to assess for respiratory motion. Using OncoFreeze, reconstruction software, we were able to apply a reconstruction algorithm to synchronize breathing with respiratory motion to reduce blur. The objective of this study is to evaluate the SUVmax of lung lesions and assess the potential difference in the values between OncoFreeze and non-OncoFreeze reconstructions. Methods: Forty-five 18F-FDG patients with active lung lesions were analyzed utilizing a within-subject design. Of the 45 studies evaluated, 78 different lung lesions were seen. The lesions were evaluated by drawing a volume of interest around the site. Each lesion’s exact positioning was classified under three categories, right or left, anterior or posterior, and segmentation of the lung. Segmentations were noted as upper, middle, or lower zones. The liver served as a baseline utilizing a mean Region of Interest (ROI). The SUVmax of each lesion were recorded using OncoFreeze and non-OncoFreeze reconstruction parameters. These values were statistically analyzed using a paired two sample t-test. Results were considered significant with the p-value less than .05. Results: OncoFreeze reconstructions demonstrated significantly higher SUVmax when compared to non-OncoFreeze values. The paired two-tailed t-test results showed a statistically significant difference between OncoFreeze and non-OncoFreeze images with a p-value of 2.9x10-10. The baseline liver ROImean was correlated with a higher value in non-OncoFreeze images. The statistical analysis of the data can be located in table 1.0. Conclusions: OncoFreeze lung lesion SUVmax were statistically significantly greater compared to non-OncoFreeze reconstructions. It should be noted that the smaller the lung lesion, the greater impact OncoFreeze reconstruction had on the SUVmax. Lung lesions less than 1 cm3 showed 30% average increased SUVmax. However, in larger regions, there was no significant difference between the values. The most notable increased values were in the middle zone lung lesions. One area of concern is the liver ROImean being slightly lower by 1.66% in OncoFreeze images warranting further research. Further implications of the study could suggest that OncoFreeze reconstructions could help provide a more accurate staging of lung cancers through PET/CT 18F-FDG images.

3058 Objectives: Primarily limited to the research environment until approximately the last decade, the development of faster scintillators, improved light collection, ever faster electronics and computing power have brought commercially available Time of Flight (TOF) Positron Emission Tomography (PET) systems into routine clinical practice.TOF technique utilizes differences in gamma photon detection timing to calculate a more accurate localization of the point of annihilation along a line-of-response. The length of the resulting segment-of-response decreases in proportion to the improvement in timing resolution. The net effect is a reduction in image noise and increased image contrast due to increased effective sensitivity - TOF PET requires fewer ‘counts’ to provide the same image contrast as non-TOF imaging. The benefits of this method are especially relevant in larger patients, where the segment-of-response is shorter than the diameter of the patient. The objective of this study is to demonstrate the benefits of the TOF technique by directly comparing images reconstructed with and without TOF. Methods: Three patients’ exams, having been clinically imaged on a Siemens Biograph Vision PET-CT system, were identified as having metastatic, F-18 FDG avid lesions. The patients’ BMIs ranged from 25-36. Per clinical protocol, each was injected with approximately 8mCi of FDG and imaged one hour post injection. BMI based total imaging time ranged from 20-25 minutes and all data sets were reconstructed with a 3D-OSEM algorithm, 4 iterations, 5 subsets and TOF (4i5s-TOF). To demonstrate the benefits of TOF, these data sets were reconstructed without TOF (4i5s-noTOF). Considering that in the absence of TOF, image quality may be improved through modification of reconstruction parameters, a third reconstruction was performed - 8i5s-noTOF. As well as a visual assessment of image quality and lesion contrast, a metastatic lesion for each patient data set was chosen for quantitative analysis (Standardized Uptake Value - SUVmax) across each of the reconstructions. To further demonstrate the enhanced image contrast provided by TOF, a background measurement (SUVavg) of adjacent normal soft tissue was included for the patient with the largest BMI. Results: For each patient, differences in reconstruction methods are immediately apparent. TOF images demonstrate increased lesion contrast (detectability) and decreased background and noise (i.e. reduced lung counts). Lesion intensity (SUVmax) with TOF is increased for each patient as counts are more accurately localized. For the largest patient, a lesion clearly visible on the TOF reconstruction becomes nearly indistinguishable from background on noTOF constructions (lesion to background ratio 89% greater with TOF versus 8i5s-noTOF). The lesion contrast with TOF was less significant for the smallest BMI patient, but still visually apparent. Results from the SUV measurements can be found in Table 1. Conclusions: In each patient, lesion contrast was considerably enhanced with TOF. This is most significantly demonstrated with the largest patient. Without TOF, the lesion nearly disappears into the background.

3052 Objectives: Conventional nuclear medicine technology requires manual daily, weekly, and monthly calibrations to be performed on SPECT systems. Technological advancements have allowed for many of Northwestern Memorial Hospital’s SPECT systems to perform quality control calibrations automatically. The objective of this study was to compare the workflow and time requirements to calibrate Siemens’ Symbia Intevo 16 with Automated Quality Control (AQC) versus quality control (QC) on the same system without automation. This work also seeks to evaluate how automated features can impact staff utilization. Methods: Multi-Head Registration (MHR) QC, performed monthly to evaluate consistency with SPECT systems, was used to compare Siemens’ Symbia Intevo AQC to manual quality control. MHR quality control using manual systems requires the technologist to prepare the point sources, select the correct collimators, choose the appropriate configuration, and position the point sources in the center of the field of view manually. AQC, however, only requires limited manual work by the technologist. The technologist must select the proper acquisition, ensure the proper collimators are on the system, and make sure the Gadolinium, a rod source stored within the system, is up to date. The system automatically positions the collimators, applies the proper configurations, and utilizes the Gadolinium rod source. Results: Although the acquisition time for each MHR quality control using systems without automated features only takes about ten minutes to complete, we found that a technologist requires about thirty minutes to prepare the point sources, set up the camera configurations and correct collimators, and wait for the QC acquisition to finish running. Variations in each point source also presented, which resulted in inconsistencies and unpredictable accuracy for each MHR manual quality control. On the other hand, the acquisition time for AQC takes places overnight. AQC only demands approximately less than five minutes of the technologist’s attention to begin the MHR quality control, depending on whether the correct collimators are on the detectors. As long as the rod source is replaced every two years, quality control delays due to Gadolinium decay can be avoided, allowing the AQC and MHR results to be completed promptly the next morning. Conclusion: In a large nuclear medicine department, like Northwestern Memorial Hospital, we found that using Automated Quality Control within Siemens’ Symbia Intevo 16 improved staff utilization. AQC most efficiently utilizes one staff member at a time with limited technologist interaction allowing for multiple camera calibrations to happen at once.

TO THE EDITOR: Recently, the Martinique Working Group (MWG), composed of representatives from the American Thyroid Association (ATA), the European Association of Nuclear Medicine (EANM), the European Thyroid Association (ETA), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI),

2067 Objectives: The presence of coronary artery calcification (CAC) may indicate plaque buildup within the arteries. CT scans are commonly used to detect CAC, and the results of these scans have been shown to have prognostic significance. Myocardial perfusion imaging (MPI) is utilized for the evaluation of patients with known or suspected coronary artery disease (CAD) by detecting areas of impaired myocardial perfusion. Some patients may have normal SPECT MPI studies, yet have calcium deposition in the coronary arteries. Thus, the objective of this study involved determining the prevalence of CAC in patients referred for SPECT MPI. Most importantly, the percentage of patients without known CAD who had CAC despite a normal SPECT MPI was determined. The early detection of CAC may affect patient treatment and minimize risk factors for CAD. Methods: SPECT and CT images from patients who underwent clinically indicated stress MPI with SPECT/CT at Northwestern Memorial Hospital were reviewed between 1/21/2018 and 12/6/2018. Patients with known CAD were excluded from the analysis. The CT images were evaluated for the presence of CAC. In patients found to have coronary calcification, the severity of the calcification was rated as mild, moderate or severe. The SPECT images were evaluated for the presence of myocardial perfusion abnormalities. Results: One hundred and one patients underwent MPI with SPECT/CT. Of these, 69 had no known CAD (41 females and 28 males, average age of 63.0 years). Coronary calcification was present in 35 patients (51%) with 19 rated as mild, 11 as moderate, and 5 as severe. Of these 69 patients, 52 had normal myocardial perfusion SPECT studies (29 females and 23 males, average age of 62.4 years). Of the patients without known CAD who had normal SPECT studies, coronary calcification was present in 26 patients (50%) with 16 rated as mild, 7 as moderate, and 3 as severe. Conclusions: These results show that approximately half of the patients without known CAD who underwent clinically ordered SPECT MPI were found to have coronary calcification, indicating the presence of subclinical CAD. A similar percentage was found even in patients with normal myocardial perfusion SPECT studies. Thus, reviewing the CT scan for the presence of coronary calcification provided information that may impact patient treatment, such as more intensive risk factor modification.