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To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50 s/mmIn an institutional review board-approved prospective study, we performed 51 whole-body DW-MRI scans in 19 children and young adults (14 males, 5 females; age range: 1-25 years) with metastasized cancers before (n = 19 scans) and after (n = 32 scans) chemotherapy. Two readers determined the presence of focal bone marrow lesions in 10 anatomical areas. A third reader measured ADC and SNR of focal lesions and normal marrow. Simultaneously acquiredThe SNR of bone marrow metastases was significantly higher compared to normal bone marrow on b = 50 s/mmBone marrow metastases in children and young adults can be equally well detected on b = 50 s/mm

Integrated 2-deoxy-2-[fluorine-18]fluoro-D-glucose (

PURPOSE: To evaluate if ferumoxytol can improve the detection of bone marrow metastases at diffusion-weighted (DW) MRI in pediatric and young adult patients with cancer. MATERIALS AND METHODS: In this secondary analysis of a prospective institutional review board–approved study (ClinicalTrials.gov identifier NCT01542879), 26 children and young adults (age range: 2–25 years; 18 males) underwent unenhanced or ferumoxytol-enhanced whole-body DW MRI between 2015 and 2020. Two reviewers determined the presence of bone marrow metastases using a Likert scale. One additional reviewer measured signal-to-noise ratios (SNRs) and tumor-to-bone marrow contrast. Fluorine 18 ((18)F) fluorodeoxyglucose (FDG) PET and follow-up chest CT, abdominal and pelvic CT, and standard (non–ferumoxytol enhanced) MRI served as the reference standard. Results of different experimental groups were compared using generalized estimation equations, Wilcoxon rank sum test, and Wilcoxon signed rank test. RESULTS: The SNR of normal bone marrow was significantly lower at ferumoxytol-enhanced MRI compared with unenhanced MRI at baseline (21.380 ± 19.878 vs 102.621 ± 94.346, respectively; P = .03) and after chemotherapy (20.026 ± 7.664 vs 54.110 ± 48.022, respectively; P = .006). This led to an increased tumor-to-marrow contrast on ferumoxytol-enhanced MRI scans compared with unenhanced MRI scans at baseline (1397.474 ± 938.576 vs 665.364 ± 440.576, respectively; P = .07) and after chemotherapy (1099.205 ± 864.604 vs 500.758 ± 439.975, respectively; P = .007). Accordingly, the sensitivity and diagnostic accuracy for detecting bone marrow metastases were 96% (94 of 98) and 99% (293 of 297), respectively, with the use of ferumoxytol-enhanced MRI compared with 83% (106 of 127) and 95% (369 of 390) with the use of unenhanced MRI. CONCLUSION: Use of ferumoxytol helped improve the detection of bone marrow metastases in children and young adults with cancer. Keywords: Pediatrics, Molecular Imaging–Cancer, Molecular Imaging–Nanoparticles, MR–Diffusion Weighted Imaging, MR Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Comparative Studies, Cancer Imaging, Ferumoxytol, USPIO © RSNA, 2023 ClinicalTrials.gov registration no. NCT01542879 See also the commentary by Holter-Chakrabarty and Glover in this issue.

Background: Growing clinical adoption of PET/MRI for prostate cancer (PC) evaluation has increased interest in reducing PET/MRI scan times. Reducing acquisition time per bed position below current times of at least 5 minutes would allow shorter examination lengths. Objective: To evaluate the effect of different reduced PET acquisition times in patients with PC who underwent 68Ga-PSMA11 or 68Ga-RM2 PET/MRI using highly sensitive silicon photomultiplier-based PET detectors. Methods: This study involved retrospective review of men with PC who underwent PET/MRI as part of one of two prospective trials. Fifty men (mean age, 69.9±6.8 years) who underwent 68Ga-RM2 PET/MRI and 50 men (66.6±5.7 years) who underwent 68Ga-PSMA11 PET/MRI were included. PET/MRI used a time-of-flight-enabled system with silicon photomultiplier-based detectors. Acquisition time was 4 minutes per bed position. PET data were reconstructed using acquisition times of 30 seconds, 1 minute, 2 minutes, 3 minutes, and 4 minutes. Three readers independently assessed image quality for each reconstruction using 1-5 scale (1=non-diagnostic; 5=excellent quality). One reader measured SUVmax for up to 6 lesions per patient. Two readers independently assessed lesion conspicuity using 1-3 scale (1=not visualized; 3=definitely visualized). Results: Mean image quality across readers at 30 seconds, 1 minutes, 2 minutes, 3 minutes, and 4 minutes was, for 68Ga-RM2 PET/MRI, 1.0±0.2 to 1.7±0.7, 2.0±0.3 to 2.6±0.8, 3.1±0.5 to 3.9±0.8, 4.6±0.6 to 4.7±0.6, and 4.8±0.4 to 4.8±0.5, respectively, and for 68Ga-PSMA11 PET/MRI was 1.2±0.4 to 1.8±0.6, 2.2±0.4 to 2.8±0.7, 3.6±0.6 to 4.1±0.8, 4.8±0.4 to 4.9±0.4, and 4.9±0.3 to 5.0±0.2, respectively. Mean lesion SUVmax for 68Ga-RM2 PET/MRI was 11.1±12.4, 10.2±11.7, 9.6±11.3, 9.5±11.6, and 9.4±11.6, respectively, and for 68Ga-PSMA11 PET/MRI was 14.7±8.2, 12.9±7.4, 12.1±7.8, 11.7±7.9, and 11.6±7.9, respectively. Mean lesion conspicuity (reader 1/reader 2) was, for 68Ga-RM2 PET/MRI, 2.4±0.5/2.7±0.5, 2.9±0.3/2.9±0.3, 3.0±0.0/3.0±0.0, 3.0±0.0/3.0±0.0, and 3.0±0.0/3.0±0.0, respectively, and for 68Ga-PSMA11 PET/MRI was 2.6±0.5/2.8±0.4, 3.0±0.2/2.9±0.3, 3.0±0.1/3.0±0.2, 3.0±0.0/3.0±0.0, and 3.0±0.0/3.0±0.0, respectively. Conclusion: Our data support routine 3 minute acquisitions, which provided very similar results as 4 minute acquisitions. Two minute acquisition, though somewhat lowering quality, provided acceptable performance and warrants consideration. Clinical Impact: When evaluating PC using modern PET/MRI equipment, time per bed position may be reduced compared with historically used times.

Please see the Editorial Comment by Javier Villanueva-Meyer discussing this article. Background: Pegfilgrastim administration after chemotherapy increases bone marrow and spleen FDG uptake. Consens...

Integrated PET/MRI has shown significant clinical value for staging and restaging of children with cancer by providing functional and anatomic tumor evaluation with a 1-stop imaging test and with up to 80% reduced radiation exposure compared with (18)F-FDG PET/CT. This article reviews clinical applications of (18)F-FDG PET/MRI that are relevant for pediatric oncology, with particular attention to the value of PET/MRI for patient management. Early adopters from 4 different institutions share their insights about specific advantages of PET/MRI technology for the assessment of young children with cancer. We discuss how whole-body PET/MRI can be of value in the evaluation of certain anatomic regions, such as soft tissues and bone marrow, as well as specific PET/MRI interpretation hallmarks in pediatric patients. We highlight how whole-body PET/MRI can improve the clinical management of children with lymphoma, sarcoma, and neurofibromatosis, by reducing the number of radiologic examinations needed (and consequently the radiation exposure), without losing diagnostic accuracy. We examine how PET/MRI can help in differentiating malignant tumors versus infectious or inflammatory diseases. Future research directions toward the use of PET/MRI for treatment evaluation of patients undergoing immunotherapy and assessment of different theranostic agents are also briefly explored. Lessons learned from applications in children might also be extended to evaluations of adult patients.

Ferumoxytol is an ultrasmall iron oxide nanoparticle, originally approved in 2009 by the FDA for IV treatment of iron deficiency in adults with chronic kidney disease. Subsequently, its off-label use as an MRI contrast agent has increased in clinical practice, particularly in pediatric patients in North America. Unlike conventional MRI contrast agents that are based on the rare earth metal gadolinium [gadolinium-based contrast agents (GBCAs)], ferumoxytol is biodegradable and carries no potential risk of nephrogenic systemic fibrosis. At FDA-approved doses, ferumoxytol demonstrates no long-term tissue retention in patients with intact iron metabolism. Ferumoxytol provides unique MRI properties including long-lasting vascular retention (facilitating high-quality vascular imaging) and retention in reticuloendothelial system tissues, thereby supporting a variety of applications beyond those possible with GBCAs. This Clinical Perspective describes clinical and early translational applications of ferumoxytol-enhanced MRI in children and young adults through off-label use for a variety of settings, including vascular, cardiac, and cancer imaging, drawing on the authors' institutional experience. In addition, we describe current preclinical and clinical research advances using ferumoxytol with regard to cellular and molecular imaging, and also as a novel potential cancer therapeutic agent.

Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.

Accurate staging and re-staging of cancer in children is crucial for patient management. Currently, children with a newly diagnosed cancer must undergo a series of imaging tests, which are stressful, time-consuming, partially redundant, expensive, and can require repetitive anesthesia. New approaches for pediatric cancer staging can evaluate the primary tumor and metastases in a single session. However, traditional one-stop imaging tests, such as CT and positron emission tomography (PET)/CT, are associated with considerable radiation exposure. This is particularly concerning for children because they are more sensitive to ionizing radiation than adults and they live long enough to experience secondary cancers later in life. In this review article we discuss child-tailored imaging tests for tumor detection and therapy response assessment - tests that can be obtained with substantially reduced radiation exposure compared to traditional CT and PET/CT scans. This includes diffusion-weighted imaging (DWI)/MRI and integrated [F-18]2-fluoro-2-deoxyglucose (18F-FDG) PET/MRI scans. While several investigators have compared the value of DWI/MRI and 18F-FDG PET/MRI for staging pediatric cancer, the value of these novel imaging technologies for cancer therapy monitoring has received surprisingly little attention. In this article, we share our experiences and review existing literature on this subject.

This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9–11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, “racial diversity in STEM,” “women in STEM,” and “global health,” which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare. Supplementary Information The online version contains supplementary material available at 10.1007/s11307-021-01610-3.

PURPOSE To determine if the correlation between different metabolic parameters along with clinical features can create an improved model of prognostication for diffuse large B-cell lymphoma (DLBCL) patients. METHODS We retrospectively evaluated 89 patients with DLBCL. All patients had a baseline and an interim 18F-FDG PET/CT. Seventy-nine also had an end-of-treatment PET/CT (EOT-PET). For each scan, we collected standardized uptake value (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmaxsum, SUVmeansum, MTVsum, and TLGsum. These metabolic parameters were combined with clinical features in order to identify a new prognostic model. The predictive value of interim PET and EOT-PET using Deauville score was also determined. RESULTS Baseline SUVmaxsum and SUVmeansum were significantly correlated to overall survival (OS) (P value = 0.012 and 0.011, respectively). The percentage change of MTV and TLG sum from baseline to EOT was predictive of progression-free survival (PFS) (P value = 0.003 and 0.022, respectively). The combination of either Deauville score at the EOT and SUVmaxsum at baseline significantly predicted OS (P value

Rationale: Novel radiopharmaceuticals for positron emission tomography (PET) are evaluated for the diagnosis of biochemically recurrent prostate cancer (BCR PC). Here, we compare the gastrin releasing peptide receptors (GRPR) - targeting 68Ga-RM2 with the prostate specific membrane antigen (PSMA) – targeting 68Ga-PSMA11 and 18F-DCFPyL. Methods: Fifty patients had both 68Ga-RM2 PET/MRI and 68Ga-PSMA11 PET/CT (n = 23) or 18F-DCFPyL PET/CT (n = 27) at an interval ranging from 1 to 60 days (mean±SD: 15.8±17.7). Maximum standardized uptake values (SUVmax) were collected for all lesions. Results: RM2 PET was positive in 35 and negative in 15 of the 50 patients. PSMA PET was positive in 37 and negative in 13 of the 50 patients. Both scans detected 70 lesions in 32 patients. Forty-three lesions in 18 patients were identified only on one scan: 68Ga-RM2 detected 7 more lesions in 4 patients, while PSMA detected 36 more lesions in 13 patients. Conclusion:68Ga-RM2 remains a valuable radiopharmaceutical even when compared with the more widely used 68Ga-PSMA11/18F-DCFPyL in the evaluation of BCR PC. Larger studies are needed to verify that identifying patients for whom these two classes of radiopharmaceuticals are complementary may ultimately allow for personalized medicine.

Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from 99mTc macroaggregated albumin (MAA) SPECT/CT with post-treatment 90Y PET/CT for absorbed dose values, and to evaluate image quality of 90Y SiPM-based PET/CT. Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning 99mTc-MAA SPECT/CT and post-therapy 90Y PET/CT were assessed. 90Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale. The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from 99mTc-MAA SPECT/CT and 90Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (P = 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (P = 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from 99mTc-MAA SPECT/CT and 90Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (P = 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (P = 0.17), respectively for resin microspheres. Image quality of 90Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively. 99mTc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of 90Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.

Pancreatic ductal adenocarcinomas (PDACs) derive from the exocrine pancreas and account for the majority of pancreatic tumors (95%). It is the seventh leading cause of cancer-related deaths and shows one of the worst prognoses in oncology with a 5-year survival rate of 9%. Pancreatic neuroendocrine tumors (pNETs) derive from the endocrine part of the pancreas. Well-differentiated pNETs are characterized by slow tumor growth and good life expectancy. In all pancreatic tumor entities, imaging plays a key role. Hybrid imaging modalities (PET/CT and PET/MRI) combine functional and structural data and may reflect a more accurate assessment of disease spread which directs subsequent treatment planning and patient management. A comprehensive search strategy was used based on PubMed and SCOPUS databases from 1999 to date. FDG PET/CT in PDAC shows high sensitivity and specificity in evaluation of T- and M-staging but lesser sensitivity of N-staging. In restaging, metabolic changes occur earlier than morphological changes in tumor size and can be assessed by molecular imaging which can act as a predictor of prognosis. 68Ga-labeled somatostatin analogs (SSAs) are the gold standard in imaging of well-differentiated pNETs. In poorly differentiated pNETs, FDG is the radiotracer of choice. PET/MRI may have added value due to higher soft-tissue contrast. However, more prospective studies comparing PET/CT and PET/MRI systems are needed. FDG PET/CT plays a key role in PDAC in staging, restaging as well as disease monitoring during follow-up. Functional imaging with 68Ga-labeled SSA is the gold standard in imaging of well-differentiated pNETs.

Highlights • 68Ga-PSMA11 PET/CT showed high detection rates for recurrent prostate cancer. • Standard and new generation PET/CT performed equally on a per-patient basis. • Delayed imaging revealed no additional lesions. • SiPM-based PET/CT identified more prostate cancer lesions. • PSMA positivity rate increased with higher PSA levels and higher PSA velocity., Objectives 68Ga-PSMA11 PET/CT is excellent for evaluating biochemically recurrent prostate cancer (BCR PC). Here, we compared the positivity rates of dual-time point imaging using a PET/CT scanner (DMI) with silicon photomultiplier (SiPM) detectors and a PET/CT scanner (D690) with photomultiplier tubes (PMT), in patients with BCR PC. Methods Fifty-eight patients were prospectively recruited and randomized to receive scans on DMI followed by D690 or vice-versa. Images from DMI were reconstructed using the block sequential regularized expectation maximization (BSREM) algorithm and images from D690 were reconstructed using ordered subset expectation maximization (OSEM), according to the vendor's recommendations. Two readers independently reviewed all images in randomized order, recorded the number and location of lesions, as well as standardized uptake value (SUV) measurements. Results Twenty-eight patients (group A) had DMI as first scanner followed by D690, while 30 patients (group B) underwent scans in reversed order. Mean PSA was 30±112.9 (range 0.3–600.66) ng/mL for group A and 41.5 ± 213.2 (range 0.21–1170) ng/mL for group B (P = 0.796). The positivity rate in group A was 78.6% (22/28 patients) vs. 73.3% (22/30 patients) in group B. Although the performance of the two scanners was equivalent on a per-patient basis, DMI identified 5 additional sites of suspected recurrent disease when used as first scanner. The second scan time point did not reveal additional abnormal uptake. Conclusions The delayed time point in 68Ga-PSMA11 PET/CT did not show a higher positivity rate. SiPM-based PET/CT identified additional lesions. Further studies with larger cohorts are needed to confirm these results.

OBJECTIVES: To compare the diagnostic accuracy of 2-[(18)F]fluoro-2-deoxy-D-glucose enhanced positron emission tomography (2-[(18)F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies. METHODS: In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8 years +/− 5.1 [standard deviation]; age range, 7–25 years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[(18)F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[(18)F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and Generalized Estimation Equation. Bone marrow biopsies and follow-up imaging served as the standard of reference. RESULTS: The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[(18)F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different “blind spots” for 2-[(18)F]FDG-PET and MRI: 2-[(18)F]FDG-PET missed sub-centimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for (18)F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[(18)F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[(18)F]FDG-PET (96.9%, p

PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent 68Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating 68Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue.

68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC. Ninety-five participants had simultaneous PET/MRI for BCR PC and were prospectively enrolled in this study. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were measured in 24 normal anatomical structures for each participant. Three readers evaluated the images independently. Uptake in various normal tissues was classified into 4 different categories: no significant uptake if SUVmean was less than SUVmean of the aortic arch (AA); mild if SUVmean was less or equal to 2.5, but higher than SUVmean of the AA; moderate if SUVmean was higher than 2.5, but less or equal to 5; intense if SUVmean was higher than 5. The most intense uptake was observed in the urinary bladder, due to excretion of the radiotracer. No significant uptake was seen in the brain, salivary glands, lungs, myocardium, skeleton, muscles, and fat. Liver, spleen, and adrenal glands had mostly no significant uptake; the gastrointestinal tract had intense physiological uptake, with pancreas being the organ with the highest SUVmax measurements (average SUVmax 64.91). Mild and moderate uptake was measured in the esophagus (average SUVmax 3.99), while the stomach wall, duodenum, and rectum had mild uptake (average SUVmax 2.49, 3.42, and 3.58, respectively). 68Ga-RM2 has been mostly evaluated for PC detection, but it can be used for other tumors overexpressing GRPR such as breast cancer. This atlas of normal biodistribution and SUV measurements in healthy tissues will help physicians distinguish between physiological vs. pathological uptake, as well as potentially assist with planning future studies using GRPR targeting radiopharmaceuticals.

To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET). Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox’s proportional hazard model were used for statistical analysis. Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS. ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

The purpose of this study is to prospectively evaluate the performance of sodium 18F]fluoride (Na[18F]F)/2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) simultaneous time-of-flight enabled positron emission tomography (PET)/magnetic resonance imaging (MRI) for the detection of skeletal metastases in selected patients with advanced breast and prostate cancers. The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. A total of 74 patients (23 women and 51 men with breast and prostate cancer, respectively) referred for standard-of-care whole-body bone scintigraphy (WBBS) were enrolled in this prospective study. All patients underwent a [99mTc]methyldiphosphonate ([99mTc]MDP) WBBS followed by Na[18F]F/[18F]FDG PET/MRI. Lesions detected by each imaging modality were tabulated and a lesion-based and patient-based analysis was conducted. On a patient-based analysis, [99mTc]MDP WBBS identified skeletal lesions in 37 patients and PET/MRI in 45 patients. On a lesion-based analysis, WBBS identified a total of 81 skeletal lesions, whereas PET/MRI identified 140 lesions. Additionally, PET/MRI showed extra-skeletal lesions in 19 patients, including lymph nodes (16), prostate (4) lung (3), and liver (2) lesions. The ability of Na[18F]F/[18F]FDG PET/MRI to identify more skeletal lesions than 99mTc-MDP WBBS and to additionally identify extra-skeletal disease may be beneficial for patient care and represent an alternative to the single modalities performed separately. Na[18F]F/[18F]FDG PET/MRI is a promising approach for evaluation of skeletal and extra-skeletal lesions in a selected population of breast and prostate cancer patients.

The usefulness of positron emission tomography/computed tomography (PET/CT) using (18F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid peptide [PEG3-E{c(RGDyk)}2] (18F-FPPRGD2) in patients with metastatic renal cell cancer (mRCC) has not been evaluated; therefore, we were prompted to conduct this pilot study. Seven patients with mRCC were enrolled in this prospective study. 18F-FPPRGD2 and 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT images were evaluated in a per-lesion analysis. Maximum standardized uptake value (SUVmax) and tumor-to-background ratio (T/B) were measured for all detected lesions, both before and after starting antiangiogenic therapy. Sixty lesions in total were detected in this cohort. SUVmax from 18F-FPPRGD2 PET/CT was lower than that from 18F-FDG PET/CT (4.4 ± 2.9 vs 7.8 ± 5.6, P

PURPOSE: To generate diagnostic (18)F-FDG PET images of pediatric cancer patients from ultra-low dose (18)F-FDG PET input images, using a novel artificial intelligence (AI) algorithm. METHODS: We used whole body (18)F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3–30 years) to developed a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose (18)F-FDG PET scans and simultaneously acquired MRI scans to produce a standard dose (18)F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans and clinical standard PET scans was evaluated by traditional metrics in computer vision, and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed rank tests and weighted kappa statistics. RESULTS: The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (p

Transarterial radioembolization (TARE) with yttrium-90 (Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planningThe mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from

PURPOSE To compare the block sequential regularized expectation maximization (BSREM) algorithm with the ordered subsets expectation maximization (OSEM) algorithm and to evaluate how different penalty factors (b values) influence image quality and SUV measurements. METHODS We analyzed data from 78 prostate cancer patients who underwent Ga-RM2 (n = 42) or Ga-prostate-specific membrane antigen (PSMA)-11 (n = 36) PET/MRI. The raw PET data were retrospectively reconstructed using both time-of-flight (TOF)-BSREM with b values of 250, 350, 500, 750, and 1000 and TOF-OSEM. Each reconstruction was reviewed independently by 3 nuclear medicine physicians and scored qualitatively using a Likert scale (1 = poor, 5 = excellent quality). SUV measurements were analyzed as well. RESULTS Fifty-seven lesions were detected (21 on Ga-RM2 and 36 on Ga-PSMA-11 PET/MRI); SUVmax decreased with the increase of β values for both tracers. Background noise (SUVsd) decreased with increasing of β values for both tracers. The mean ± SD scores for Ga-RM2 PET images were 2.4 ± 0.5 for b = 250 reconstructions, 3.2 ± 0.6 for b = 350, 4 ± 0.6 for b = 500, 4.5 ± 0.5 for b = 750, 4.4 ± 0.7 for b = 1000, and 3.4 ± 0.6 for TOF-OSEM. The mean ± SD scores for Ga-PSMA-11 PET images were 3.2 ± 0.8 for b = 250 reconstructions, 4.1 ± 0.8 for b = 350, 4.7 ± 0.6 for b = 500, 4.8 ± 0.4 for b = 750, 4.7 ± 0.6 for b = 1000, and 3.8 ± 0.5 for TOF-OSEM. CONCLUSIONS Time-of-flight-BSREM algorithm improves image quality. Different b values should be used for different Ga-labeled radiopharmaceuticals such as those targeting GRPR and PSMA receptors. Once selected, the same b value should be consistently used because SUVmax measurements differ with different b values.

Introduction:68Ga-RM2 is a synthetic bombesin receptor antagonist targeting gastrin-releasing peptide receptors (GRPr) that are overexpressed in several human tumors, including prostate cancer (PC)...

OBJECTIVE. Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even ...

Targeting tumor-expressed receptors using selective molecules for diagnostic, therapeutic, or both diagnostic and therapeutic (theragnostic) purposes is a promising approach in oncologic applications. Such approaches have increased significantly over the past decade. Peptides such as gastrin-releasing peptide receptors targeting radiopharmaceuticals are small molecules with fast blood clearance and urinary excretion. They demonstrate good tissue diffusion, low immunogenicity, and highly selective binding to their target cell-surface receptors. They are also easily produced. Gastrin-releasing peptide receptors, part of the bombesin family, are overexpressed in many tumors, including breast and prostate cancer, and therefore represent an attractive target for future development.

Pancreas cancer is a complex disease and its prognosis is related to the origin of the tumor cell as well as the stage of disease at the time of diagnosis. Pancreatic adenocarcinomas derive from the exocrine pancreas and are the fourth leading cause of cancer-related deaths in the United States, while well-differentiated pancreatic neuroendocrine tumors (pNETs) derived from the endocrine part of the pancreas are rare and characterized by a slow growth and good life expectancy. Surgery is the only curative treatment approach, and an accurate assessment of resectability is of paramount importance in order to avoid futile procedures. The role of molecular imaging with positron emission tomography and computed tomography ranges from indispensable for pNETs to controversial for certain scenarios in pancreatic adenocarcinomas. This review article aims to overview molecular pancreatic imaging.

OBJECTIVE To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0. METHODS We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria. RESULTS The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively). CONCLUSIONS The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.

Nuclear medicine can play an important role in evaluating prostate cancer combining anatomical and functional information with hybrid techniques. Various PET radiopharmaceuticals have been used for targeting specific biological markers in prostate cancer. Research is ideally oriented towards the development of radiopharmaceuticals targeting antigens overexpressed in prostate cancer, as opposed to normal prostate tissue. In this regard, gastrin-releasing peptide receptors (GRPR) are excellent candidates. Bombesin analogues targeting the GRPR have been investigated. Gallium-68 (68Ga) is an interesting PET radioisotope due to several advantages, such as availability, ease of radiochemistry, half-life, and costs. The focus of this review is on 68Ga-labeled bombesin analogues in prostate cancer.