Search

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...

A novel cystine-knot peptide–based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin αvβ6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer. Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7–14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean

18F-DCFPyL was recently approved by the FDA for evaluation prior to definitive therapy and for biochemical recurrence. Here we focus on the key data that justify the clinical use of 18F-DCFPyL, as well as those aspects of protocol implementation and image interpretation that are important to the nuclear medicine physicians and radiologists who will interpret 18F-DCFPyL PET/CT and PET/MR scans.

Post-transplant lymphoproliferative disorders (PTLD) are a spectrum of heterogeneous lymphoproliferative conditions that are serious and possibly fatal complications after solid organ or allogenic hematopoietic stem cell transplantation. Most PTLD are attributed to Epstein-Barr virus reactivation in B-cells in the setting of immunosuppression after transplantation. Early diagnosis, accurate staging, and timely treatment are of vital importance to reduce morbidity and mortality. Given the often nonspecific clinical presentation and disease heterogeneity of PTLD, tissue biopsy and histopathological analysis are essential to establish diagnosis and most importantly, determine the subtype of PTLD, which guides treatment options. Advanced imaging modalities such as 18F-FDG PET/CT have played an increasingly important role and have shown high sensitivity and specificity in detection, staging, and assessing treatment response in multiple clinical studies over the last two decades. However, larger multicenter prospective validation is still needed to further establish the clinical utility of PET imaging in the management of PTLD. Significantly, new hybrid imaging modalities such as PET/MR may help reduce radiation exposure, which is especially important in pediatric transplant patients.

Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

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.

Purpose: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen–targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging. Experimental Design: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety. Results: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2–98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%–87.0% (lower bound of 95% CI: 77.8–80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers). Conclusions: Performance of 18F-DCFPyL-PET/CT achieved the study’s primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer. See related commentary by True and Chen, p. 3512

Purpose: To investigate the prognostic value of 18F-FDG PET/CT parameters in melanoma patients before beginning anti-PD-1 therapy. Methods: Imaging parameters including SUVmax, metabolic tumor volume (MTV), and bone marrow to liver SUVmean ratio (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. Association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data between high (> median) and low (≤ median) BLR groups were compared. Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for PFS and OS (P = 0.017, P = 0.011, respectively). The high BLR group had higher levels of white blood cell count/neutrophil count and C-Reactive Protein than the low BLR group (P < 0.05). Conclusion: Patients with high BLR were associated with poor PFS and OS, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.

To evaluate the diagnostic performance and clinical utility of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). 18F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging (18F-NaF PET/CT (n = 12), 68Ga-PSMA11 PET/CT (n = 5), 18F-DCFPyL PET/CT (n = 20), and 68Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated. The overall positivity rate of 18F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA

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.

18F-FDG-PET is complementary to conventional imaging in patients with clinical suspicion for exocrine pancreatic malignancies. It has similar if not superior sensitivity and specificity for detection of cancer, and when combined with contrast enhanced anatomic imaging of the abdomen, can improve diagnostic accuracy and aid in staging, assessment for resectability, radiation therapy planning, and prognostication. Various metabolic pathways affect FDG uptake in pancreatic ductal adenocarcinoma. The degree of uptake reflects histopathology, aggressiveness, metastatic potential, and metabolic profile of malignant cell and their interaction with cancer stroma. After treatment, FDG-PET is useful for detection of residual or recurrent cancer and can be used to assess and monitor response to therapy in unresectable or metastatic disease. The degree and pattern of uptake combined with other imaging features are useful in characterization of incidental pancreatic lesions and benign processes such as inflammation. Several novel PET radiopharmaceuticals have been developed to improve detection and management of pancreatic cancer. Gallbladder carcinoma is typically FDG avid and when anatomic imaging is equivocal PET can be used to assess metastatic involvement with high specificity and inform subsequent management.

We investigated the ability of baseline 2-deoxy-2-[18F]fluoro-d-glucose PET/CT parameters, acquired before the start of immunotherapy, to predict development of hyperprogressive disease (HPD) in melanoma patients. We also evaluated the diagnostic performances of ratios of baseline and first restaging PET/CT parameters to diagnose HPD without information of the tumor growth kinetic ratio (TGKR) that requires pre-baseline imaging before baseline imaging (3 timepoint imaging). Seventy-six patients who underwent PET/CT before and approximately 3 months following initiation of immunotherapy were included. PET/CT parameters, including metabolic tumor volume (MTV) for all melanoma lesions and total measured tumor burden (TMTB) based on irRECIST, were measured from baseline PET/CT (MTVbase and TMTBbase) and first restaging PET/CT (MTVpost and TMTBpost). The ratios of MTV (MTVpost/MTVbase, MTVr) and TMTB (TMTBpost/TMTBbase, TMTBr) were calculated. MTVbase of HPD patients (n = 9, TGKR ≥ 2) was larger than that of non-HPD (n = 67, TGKR

To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR). A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models’ performances were evaluated on independent test datasets. For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p

To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers. We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software. All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq. We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731. ClinicalTrials.gov , NCT03539731 (registered 28 May 2018)

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.

PET/MR imaging is in routine clinical use and is at least as effective as PET/CT for oncologic and neurologic studies with advantages with certain PET radiopharmaceuticals and applications. In addition, whole body PET/MR imaging substantially reduces radiation dosages compared with PET/CT which is particularly relevant to pediatric and young adult population. For cancer imaging, assessment of hepatic, pelvic, and soft-tissue malignancies may benefit from PET/MR imaging. For neurologic imaging, volumetric brain MR imaging can detect regional volume loss relevant to cognitive impairment and epilepsy. In addition, the single-bed position acquisition enables dynamic brain PET imaging without extending the total study length which has the potential to enhance the diagnostic information from PET.

International audience

Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.

The high-background glucose metabolism of normal gray matter on [18F]-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) of the brain results in a low signal-to-background ratio, potentially increasing the possibility of missing important findings in patients with intracranial malignancies. To explore the strategy of using a deep learning classifier to aid in distinguishing normal versus abnormal findings on PET brain images, this study evaluated the performance of a two-dimensional convolutional neural network (2D-CNN) to classify FDG PET brain scans as normal (N) or abnormal (A). Methods: Two hundred eighty-nine brain FDG-PET scans (N; n = 150, A; n = 139) resulting in a total of 68,260 images were included. Nine individual 2D-CNN models with three different window settings for axial, coronal, and sagittal axes were trained and validated. The performance of these individual and ensemble models was evaluated and compared using a test dataset. Odds ratio, Akaike’s information criterion (AIC), and area under curve (AUC) on receiver-operative-characteristic curve, accuracy, and standard deviation (SD) were calculated. Results: An optimal window setting to classify normal and abnormal scans was different for each axis of the individual models. An ensembled model using different axes with an optimized window setting (window-triad) showed better performance than ensembled models using the same axis and different windows settings (axis-triad). Increase in odds ratio and decrease in SD were observed in both axis-triad and window-triad models compared with individual models, whereas improvements of AUC and AIC were seen in window-triad models. An overall model averaging the probabilities of all individual models showed the best accuracy of 82.0%. Conclusions: Data ensemble using different window settings and axes was effective to improve 2D-CNN performance parameters for the classification of brain FDG-PET scans. If prospectively validated with a larger cohort of patients, similar models could provide decision support in a clinical setting.

18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52–91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18F-fluciclovine PET/CT (18), or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results:18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA

Objective: To harmonize multicenter 89Zr PET imaging for oncology trials and to evaluate lesion detection. Methods: Seven PET scanners were evaluated using a custom chest oncology phantom with nine spherical lesions, 7-20 mm in diameter. A 4:1 lesion to background ratio simulating a patient dose of 92.5 MBq. Various image reconstructions were evaluated. Images were assessed for lesion detection and recovery coefficients (RC) and background signal variance were measured. Results: Two scanners failed to meet the quality control criteria. Optimal reconstruction algorithms enabling adequate lesion detection and reliable quantification across the other five scanners were determined without compromising the data quality. On average, 95% of the 10 mm lesions were detected and the 7 mm lesion was visualized in only one scanner. The background variance range was 8.6 to 16%. Conclusion: We established multicenter harmonization procedures for 89Zr PET imaging in oncology, optimizing small lesion (≥10 mm) detectability and accurate quantification.

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.

Since the introduction of simultaneous PET/MRI in 2011, there have been significant advancements. In this review, we highlight several technical advancements that have been made primarily in attenuation and motion correction and discuss the status of multiple clinical applications using PET/MRI. This review is based on the experience at the first PET/MRI conference cosponsored by the International Society for Magnetic Resonance in Medicine and the Society of Nuclear Medicine and Molecular Imaging.

Background: Cardiac fluorodeoxyglucose positron-emission tomography (FDG-PET) has emerged as a standard imaging modality for the diagnosis of cardiac sarcoidosis (CS); however, there is a scarcity of data on the use of serial FDG-PET to guide immunosuppressive therapy. The aim of this work was to report our experience using serial FDG-PET for the diagnosis and management of patients with CS, focusing on its utility in ongoing immunosuppression management. Methods and Results: We studied consecutive patients with CS managed at Stanford University from 2010 to 2017. We evaluated our experience using FDG-PET for diagnosis and guidance of immunosuppressive therapy titration in CS. Among 34 patients diagnosed with CS, 16 (47%), 12 (35%) and 14(41%) presented with heart block, heart failure, and ventricular arrhythmias, respectively. FDG-PET proved beneficial in the initial diagnosis in 21 patients (62%). A total of 128 FDG-PET scans were performed (median 3 per patient). Ninety-four FDG-PET scans (73%) resulted in a change in therapy, with 42FDG-PET scans (33%) instrumental for tapering prednisone. Among patients who were initiated on prednisone, the mean dose of prednisone at 1 year was 9.5mg/d. Over a median follow-up of 2.3years, 48% of patients were successfully weaned from prednisone completely, and 20% were weaned to a maintenance dosage of 5–10mg/d. During the follow-up period, transplant-free survival was 88%. Conclusions: The use of serial cardiac FDG-PET for the diagnosis and management of CS was critical for guiding immunosuppression management and resulted in low chronic steroid doses and good disease control within 1 year of diagnosis.

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

The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hurthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E-mutated anaplastic thyroid carcinoma.

Lutetium-177 ( 177 Lu)-DOTATATE is an effective systemic therapy for metastatic somatostatin receptor positive neuroendocrine tumors (NETs). Here we report our experience with the use of pre-therapy 68 Ga-DOTATATE PET as prognostic marker for short-term clinical outcomes of 177 Lu-DOTATATE therapy in patients with advanced NETs. Materials and methods: We retrospectively reviewed patients who received at least one dose of 177 Lu-DOTATATE between Dec. 2016 and July 2019 at our institution. 50 patients (63.6 ± 10.0 years) with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who had pre-therapy 68 Ga-DOTATATE PET were included in the analysis. 68 Ga-DOTATATE avid tumor volumes were determined automatically using an SUV thresholding approach. Total and extrahepatic 68 Ga-DOTATATE avid tumor volumes were measured and dichotomized into large and small tumor volume groups. Association with progression free survival (PFS) and overall survival (OS) were determined at median follow up of 32 months by Kaplan-Meier survival analysis with Log-Rank test. Results: During follow up, 38 patients (76%) had disease progression and 15 patients (30%) died. Kaplan-Meier analysis of PFS in GEP-NETs patients showed that smaller extrahepatic 68 Ga-DOTATATE avid tumor volume ( 1000 mL) tumor volumes, no statistically significant difference in PFS is observed, P = 0.19. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate at 58% and 72%. Conclusions: Smaller extrahepatic 68 Ga-DOTATATE avid tumor volumes are associated with longer PFS and OS following 177 Lu-DOTATATE treatment in patients with advanced GEP-NETs. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate, which may limit its clinical application.

Purpose/objective(s) The X1 system ("X1") integrates a fully functional Positron Emission Tomography (PET) combined with a fan-beam kVCT system into the architecture of a ring-gantry linear accelerator (LINAC) for biology-guided radiotherapy (BgRT) delivery. The integration of PET into a LINAC framework required design features that deviate from the diagnostic setting. For instance, the X1 houses two opposed 90° PET arcs that rotate at 60 RPM to generate sinogram reconstructed images rather than a static, circumferential array of detectors. To better understand X1 PET performance, we conducted a side-by-side comparison of images of a PET phantom obtained sequentially on the X1 PET subsystem and a traditional PET/CT scanner. Materials/methods An independent quality assurance phantom utilized a custom insert with two-insert targets filled with 18F-fluorodeoxyglucose (FDG) diluted water. Spherical target had a diameter of 22 mm and C-shape geometry consisted of an active volume of 26mm axial length and 255-degree partial annulus with major and minor radii of 27 mm x 12 mm, respectively. The targets were filled with an activity concentration of 9.3 kBq/ml to achieve a target to background ratio of 8:1 simulating the target uptake with hot background in a patient. The phantom was imaged within 30 minutes of preparation on the X1 PET and then immediately transferred to a PET/CT Biograph scanner for a second image. This experiment was repeated three times in separate days to assess reproducibility of PET acquisition. The PET images were visually assessed by the radiation oncologists to ensure the PET signal is within PTV. The PET signals of the targets were also evaluated using the full-width-half-max (FWHM) calculated on left-right (RL), anterior-posterior (AP) and superior-inferior (SI) directions for both targets and compared to the physical dimensions of the cavities. Results The imaging acquisition tests were successfully completed on all three days for both systems, as per the prescribed workflow. In all experiments, radiation oncologists verified that the PET avid area were within the PTV in both systems. Average FWHM results of the 22 mm spherical target on X1 PET were 24.5, 21.7 and 17.0 mm as compared to 20.0, 20.0 and 18.2 mm for PET/CT in LR, AP and SI directions, respectively. For the C-shape object X1 PET resulted in 18.8, 19.5, 21.8 and 25.0 mm whereas the PET/CT resulted in 12.7, 13.2, 13.2 and 24.7 mm FWHMs for the two RL C-shape legs, AP and SI directions, respectively as compared to 15-, 15-, 15- and 26-mm physical dimensions. Conclusion The X1 PET subsystem - which utilizes dual PET arcs and a sinogram image reconstruction algorithm in order to integrate into a LINAC architecture - generates images that are qualitatively comparable to a traditional PET scanner. In general, X1 FWHM results were slightly larger and PET/CT ones were smaller than the physical dimensions in axial plane. Both systems slightly underestimated the target size in SI direction.

The objective of this review was to explore the potential clinical application of unconventional non-amino acid PET radiopharmaceuticals in patients with gliomas. A comprehensive search strategy was used based on SCOPUS and PubMed databases using the following string: (“perfusion” OR “angiogenesis” OR “hypoxia” OR “neuroinflammation” OR proliferation OR invasiveness) AND (“brain tumor” OR “glioma”) AND (“Positron Emission Tomography” OR PET). From all studies published in English, the most relevant articles were selected for this review, evaluating the mostly used PET radiopharmaceuticals in research centers, beyond amino acid radiotracers and 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG), for the assessment of different biological features, such as perfusion, angiogenesis, hypoxia, neuroinflammation, cell proliferation, tumor invasiveness, and other biological characteristics in patients with glioma. At present, the use of non-amino acid PET radiopharmaceuticals specifically designed to assess perfusion, angiogenesis, hypoxia, neuroinflammation, cell proliferation, tumor invasiveness, and other biological features in glioma is still limited. The use of investigational PET radiopharmaceuticals should be further explored considering their promising potential and studies specifically designed to validate these preliminary findings are needed. In the clinical scenario, advancements in the development of new PET radiopharmaceuticals and new imaging technologies (e.g., PET/MR and the application of the artificial intelligence to medical images) might contribute to improve the clinical translation of these novel radiotracers in the assessment of gliomas.

The recently presented and published results of the VISION phase III study of 177Lu-PSMA617 for metastatic castration-resistant prostate cancer ([ 1 ][1]) are indeed one of the greatest success stories in the history of nuclear medicine ([ 2 ][2]). They add to the earlier experiences from first-in

Despite significant advances in detection and treatment, prostate cancer (PC) remains the most common malignancy and a major cause of cancer death in men worldwide. Imaging is critically important for the diagnosis, staging, and management of men with prostate cancer (PC). The conventional imaging modalities have been employed for local and metastatic staging with limited performance. Whole-body positron emission tomography (PET) using prostate membrane antigen-based tracers is the most widely used in research and clinical applications in this scenario. However, other ways to image PC are available. Here, we review the clinical literatures on the use of gastrin-releasing peptide receptors (GRPRs) as targets for imaging patients with PC.

ObjectivesTo describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs).MethodsClinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases.ResultsThis study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%).ConclusionThis study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

TO THE EDITOR: We read with interest the article by Bucknor et al. titled, “Disparities in PET Imaging for Prostate Cancer at a Tertiary Academic Medical Center” ([1][1]). The authors compare enrollment data between 2 cohorts: one having standard-of-care (SOC) 18F-fluciclovine PET and a second

The role of molecular imaging in initial evaluation of men with presumed or established diagnosis of prostate cancer and work up of biochemical recurrence and metastatic disease is rapidly evolving due to superior diagnostic performance compared to anatomic imaging. However, variable tumor biology and expression of transmembrane proteins or metabolic alterations poses a challenge. We review the evidence and controversies with emphasis on emerging PET radiopharmaceuticals and experience on clinical utility of PET/CT and PET/MRI in diagnosis and management of prostate cancer.

Gliomas, particularly high-grade gliomas including glioblastoma (GBM), represent the most common and malignant types of primary brain cancer in adults, and carry a poor prognosis. GBM has been classified into distinct subgroups over the years based on cellular morphology, clinical characteristics, biomarkers, and neuroimaging findings. Based on these classifications, differences in therapeutic response and patient outcomes have been established. Recently, the identification of complex molecular signatures of GBM has led to the development of diverse targeted therapeutic regimens and translation into multiple clinical trials. Chemical-, peptide-, antibody-, and nanoparticle-based probes have been designed to target specific molecules in gliomas and then be visualized with multimodality molecular imaging (MI) techniques including positron emission tomography (PET), single-photon emission computed tomography (SPECT), near-infrared fluorescence (NIRF), bioluminescence imaging (BLI), and magnetic resonance imaging (MRI). Thus, multiple molecules of interest can now be noninvasively imaged to guide targeted therapies with a potential survival benefit. Here, we review developments in molecular-targeted diagnosis and therapy in glioma, MI of these targets, and MI monitoring of treatment response, with a focus on the biological mechanisms of these advanced molecular probes. MI probes have the potential to noninvasively demonstrate the pathophysiologic features of glioma for diagnostic, treatment, and response assessment considerations for various targeted therapies, including immunotherapy. However, most MI tracers are in preclinical development, with only integrin αVβ3 and isocitrate dehydrogenase (IDH)-mutant MI tracers having been translated to patients. Expanded international collaborations would accelerate translational research in the field of glioma MI.

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:Improved diagnostics are needed to better inform the treatment of men with biochemically recurrent (BCR) prostate cancer (PCa). 18F-DCFPyL is a novel PET agent that selectively binds w...

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)...

Purpose of review The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA). Recent findings Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface. Summary Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.

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 ...