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Meta-[ 123 I]iodobenzylguanidine ([ 123 I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [ 123 I]MIBG with the new PET tracer meta-[ 18 F]fluorobenzylguanidine ([ 18 F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [ 18 F]MFBG LAFOV PET/CT and compare it with [ 123 I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [ 123 I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [ 123 I]MIBG scintigraphy and SPECT/low-dose CT, [ 18 F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [ 123 I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [ 18 F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [ 18 F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [ 123 I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [ 18 F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [ 18 F]MFBG LAFOV PET/CT compared with [ 123 I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [ 18 F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Diagnosing relapse after radiotherapy for lung cancer is challenging. The specificity of both CT and 18 F-FDG PET/CT is low because of radiation-induced changes. 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) PET has previously demonstrated higher specificity for malignancy than 18 F-FDG PET. We investigated the value of 18 F-FLT PET/CT for diagnosing relapse in irradiated lung cancer. Methods: Patients suspected of relapse of lung cancer after definitive radiotherapy (conventional fractionated radiotherapy [cRT] or stereotactic body radiotherapy [SBRT]) were included. Sensitivity and specificity were analyzed both within the irradiated high-dose volume (HDV) and on a patient basis. Marginal differences and interobserver agreement were assessed. Results: Sixty-three patients who had received radiotherapy in 70 HDVs (34 cRT; 36 SBRT) were included. The specificity of 18 F-FLT PET/CT was higher than that of 18 F-FDG PET/CT (HDV, 96% [95% CI, 87-100] vs. 71% [95% CI, 57-83] [ P = 0.0039]; patient-based, 90% [95% CI, 73-98] vs. 55% [95% CI, 36-74] [ P = 0.0020]). The difference in specificity between 18 F-FLT PET/CT and 18 F-FDG PET/CT was higher after cRT than after SBRT. The sensitivity of 18 F-FLT PET/CT was lower than that of 18 F-FDG PET/CT (HDV, 69% [95% CI, 41-89] vs. 94% [95% CI, 70-100] [ P = 0.1250]; patient-based, 70% [95% CI, 51-84] vs. 94% [95% CI, 80-99] [ P = 0.0078]). Adding 18 F-FLT PET/CT when 18 F-FDG PET/CT was positive or inconclusive improved the diagnostic value compared with 18 F-FDG PET/CT alone. In cRT HDVs, the probability of malignancy increased from 67% for 18 F-FDG PET/CT alone to 100% when both tracers were positive. Conclusion: 18 F-FLT PET/CT adds diagnostic value to 18 F-FDG PET/CT in patients with suspected relapse. The diagnostic impact of 18 F-FLT PET/CT was highest after cRT. We suggest adding 18 F-FLT PET/CT when 18 F-FDG PET/CT is inconclusive or positive within the previously irradiated volume to improve diagnostic value in patients for whom histologic confirmation is not easily obtained., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The aim of this study was to evaluate the correlation between uptake of the PET ligand 68 Ga-NOTA-AE105, targeting the urokinase-type plasminogen activator receptor (uPAR), and Gleason score in patients undergoing prostate biopsy. Methods: Patients with clinical suspicion of prostate cancer (PCa) or previously diagnosed with PCa were prospectively enrolled in this phase 2 trial. A combination of uPAR PET and multiparametric MRI (mpMRI) was performed, and the SUV in the primary tumor, as delineated by mpMRI, was measured by 2 independent readers. The correlation between the SUV and the Gleason score obtained by biopsy was assessed. Results: A total of 27 patients had histologically verified PCa visible on mpMRI and constituted the study population. There was a positive correlation between the SUV max and the Gleason score (Spearman ρ = 0.55; P = 0.003). Receiver operating characteristic analysis showed an area under the curve of 0.88 (95% CI, 0.67-1.00) for discriminating a Gleason score of greater than or equal to 3 + 4 from a Gleason score of less than or equal to 3 + 3. A cutoff for the tumor SUV max could be established with a sensitivity of 96% (79%-99%) and a specificity of 75% (30%-95%) for detecting a Gleason score of greater than or equal to 3 + 4. For discriminating a Gleason score of greater than or equal to 4 + 3 from a Gleason score of less than or equal to 3 + 4, a cutoff could be established for detecting a Gleason score of greater than or equal to 4 + 3 with a sensitivity of 93% (69%-99%) and a specificity of 62% (36%-82%). Conclusion: SUV measurements from uPAR PET in primary tumors, as delineated by mpMRI, showed a significant correlation with the Gleason score, and the tumor SUV max was able to discriminate between low-risk Gleason score profiles and intermediate risk Gleason score profiles with a high diagnostic accuracy. Consequently, uPAR PET/MRI could be a promising method for the noninvasive evaluation of PCa and might reduce the need for repeated biopsies (e.g., in active surveillance)., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

64 Cu-DOTATATE PET/CT imaging 1 h after injection is excellent for lesion detection in patients with neuroendocrine neoplasms (NENs). We hypothesized that the imaging time window can be extended up to 3 h after injection without significant differences in the number of lesions detected. Methods: From a prospective study, we compared, on a head-to-head basis, sets of 64 Cu-DOTATATE PET/CT images from 35 patients with NENs scanned 1 and 3 h after injection of 200 MBq of 64 Cu-DOTATATE. The number of lesions on both PET scans was counted and grouped according to organs or regions and compared with negative binomial regression. Discordant lesions (visible on only the 1-h images or only the 3-h 64 Cu-DOTATATE PET images) were considered true if found on simultaneous CT or later MR, CT, or somatostatin receptor imaging. We measured lesion SUV max , reference normal-organ or -tissue SUV mean , and tumor-to-normal-tissue ratios calculated from SUV max and SUV mean Results: We found 822 concordant lesions (visible on both 1-h and 3-h 64 Cu-DOTATATE PET) and 5 discordant lesions, of which 4 were considered true. One discordant case in 1 patient involved a discordant organ system (lymph node) detected on 3-h but not 1-h 64 Cu-DOTATATE PET that did not alter the patient's disease stage (stage IV) because the patient had 11 additional concordant liver lesions. We found no significant differences between the number of lesions detected on 1-h and 3-h 64 Cu-DOTATATE PET. Throughout the 1- to 3-h imaging window, the mean tumor-to-normal-tissue ratio remained high in all key organs: liver (1 h: 12.6 [95% confidence interval (CI), 10.2-14.9]; 3 h: 11.0 [95%CI, 8.7-13.4]), intestines (1 h: 24.2 [95%CI, 14.9-33.4]; 3 h: 28.2 [95%CI, 16.5-40.0]), pancreas (1 h: 42.4 [95%CI, 12.3-72.5]; 3 h: 41.1 [95%CI, 8.7-73.4]), and bone (1 h: 103.0 [95%CI, 38.6-167.4]; 3 h: 124.2 [95%CI, 57.1-191.2]). Conclusion: The imaging time window of 64 Cu-DOTATATE PET/CT for patients with NENs can be expanded from 1 h to 1-3 h without significant differences in the number of lesions detected., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The purpose of this study was to investigate and assess the correlation and reproducibility of multiparametric imaging in head and neck cancer patients., Methods: Twenty-one patients were included in this prospective scan-rescan study. All patients were scanned twice on an integrated PET and MRI scanner. Gross tumor volumes were defined on T2-weighted MR images, and volumes of interest were defined on diffusion-weighted MRI and 18 F-FDG PET (VOI DWI , VOI PET ). Overlap between volumes was assessed as a percentwise overlap. 18 F-FDG uptake and diffusion were measured using SUV and apparent diffusion coefficient, and correlation was tested across and within patients and as a voxel-by-voxel analysis., Results: Seventeen patients were available for correlation analysis, and 12 patients were available for assessment of tumor overlap. The median tumor overlap between VOI DWI and VOI PET was 82% (VOI DWI in VOI PET ) and 62% (VOI PET in VOI DWI ) on scan 1 and scan 2, respectively. Across patients, the correlation between SUV and apparent diffusion coefficient was weak and nonsignificant. However, in individual patients a weak but significant correlation was identified on a voxel-by-voxel basis., Conclusion: In multiparametric imaging with the integrated PET/MR scanner, the VOIs from DWI and 18 F-FDG PET were both within the target volume for radiotherapy and overlapped substantially although not completely. No correlation between 18 F-FDG uptake and DWI could be found across patients, but within individual patients a statistically significant, but weak, voxel-by-voxel correlation was found. The findings suggest that information on glucose uptake and diffusion coefficient carries complementary information of interest that may be relevant for radiotherapy treatment planning., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: With the introduction of combined PET/MR spectroscopic (MRS) imaging, it is now possible to directly and indirectly image the Warburg effect with hyperpolarized (13)C-pyruvate and (18)F-FDG PET imaging, respectively, via a technique we have named hyperPET. The main purpose of this present study was to establish a practical workflow for performing (18)F-FDG PET and hyperpolarized (13)C-pyruvate MRS imaging simultaneously for tumor tissue characterization and on a larger scale test its feasibility. In addition, we evaluated the correlation between (18)F-FDG uptake and (13)C-lactate production., Methods: Ten dogs with biopsy-verified spontaneous malignant tumors were included for imaging. All dogs underwent a protocol of simultaneous (18)F-FDG PET, anatomic MR, and hyperpolarized dynamic nuclear polarization with (13)C-pyruvate imaging. The data were acquired using a combined clinical PET/MR imaging scanner., Results: We found that combined (18)F-FDG PET and (13)C-pyruvate MRS imaging was possible in a single session of approximately 2 h. A continuous workflow was obtained with the injection of (18)F-FDG when the dogs was placed in the PET/MR scanner. (13)C-MRS dynamic acquisition demonstrated in an axial slab increased (13)C-lactate production in 9 of 10 dogs. For the 9 dogs, the (13)C-lactate was detected after a mean of 25 s (range, 17-33 s), with a mean to peak of (13)C-lactate at 49 s (range, 40-62 s). (13)C-pyruvate could be detected on average after 13 s (range, 5-26 s) and peaked on average after 25 s (range, 13-42 s). We noticed concordance of (18)F-FDG uptake and production of (13)C-lactate in most, but not all, axial slices., Conclusion: In this study, we have shown in a series of dogs with cancer that hyperPET can easily be performed within 2 h. We showed mostly correspondence between (13)C-lactate production and (18)F-FDG uptake and expect the combined modalities to reveal additional metabolic information to improve prognostic value and improve response monitoring., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)