Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.

OBJECTIVES: Tumor dosimetry with somatostatin receptor-targeted peptide receptor radionuclide therapy (SSTR-targeted PRRT) by 177Lu-DOTATATE may contribute to improved treatment monitoring of refractory meningioma. Accurate dosimetry requires reliable and reproducible pretherapeutic PET tumor segmentation which is not currently available. This study aims to propose semi-automated segmentation methods to determine metabolic tumor volume with pretherapeutic 68Ga-DOTATOC PET and evaluate SUVmean-derived values as predictive factors for tumor-absorbed dose. METHODS: Thirty-nine meningioma lesions from twenty patients were analyzed. The ground truth PET and SPECT volumes (VolGT-PET and VolGT-SPECT) were computed from manual segmentations by five experienced nuclear physicians. SUV-related indexes were extracted from VolGT-PET and the semi-automated PET volumes providing the best Dice index with VolGT-PET (Volopt) across several methods: SUV absolute-value (2.3)-threshold, adaptative methods (Jentzen, Otsu, Contrast-based method), advanced gradient-based technique, and multiple relative thresholds (% of tumor SUVmax, hypophysis SUVmean, and meninges SUVpeak) with optimal threshold optimized. Tumor-absorbed doses were obtained from the VolGT-SPECT, corrected for partial volume effect, performed on a 360° whole-body CZT-camera at 24, 96, and 168 h after administration of 177Lu-DOTATATE. RESULTS: Volopt was obtained from 1.7-fold meninges SUVpeak (Dice index 0.85 ± 0.07). SUVmean and total lesion uptake (SUVmeanxlesion volume) showed better correlations with tumor-absorbed doses than SUVmax when determined with the VolGT (respective Pearson correlation coefficients of 0.78, 0.67, and 0.56) or Volopt (0.64, 0.66, and 0.56). CONCLUSION: Accurate definition of pretherapeutic PET volumes is justified since SUVmean-derived values provide the best tumor-absorbed dose predictions in refractory meningioma patients treated by 177Lu-DOTATATE. This study provides a semi-automated segmentation method of pretherapeutic 68Ga-DOTATOC PET volumes to achieve good reproducibility between physicians. CLINICAL RELEVANCE STATEMENT: SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET are predictive of tumor-absorbed doses in refractory meningiomas treated by 177Lu-DOTATATE, justifying to accurately define pretherapeutic PET volumes. This study provides a semi-automated segmentation of 68Ga-DOTATOC PET images easily applicable in routine. KEY POINTS: • SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET images provide the best predictive factors of tumor-absorbed doses related to 177Lu-DOTATATE PRRT in refractory meningioma. • A 1.7-fold meninges SUVpeak segmentation method used to determine metabolic tumor volume on pretherapeutic 68Ga-DOTATOC PET images of refractory meningioma treated by 177Lu-DOTATATE is as efficient as the currently routine manual segmentation method and limits inter- and intra-observer variabilities. • This semi-automated method for segmentation of refractory meningioma is easily applicable to routine practice and transferrable across PET centers.

Detection of acute myocarditis by ECG-triggered PET imaging of somatostatin receptors compared to cardiac magnetic resonance: preliminary results.

Somatostatin receptors are overexpressed by inflammatory cells but not by cardiac cells, under normal conditions. This study assesses the detection of acute myocarditis by the ECG-triggered digital-PET imaging of somatostatin receptors (68Ga-DOTATOC-PET), as compared to Cardiac Magnetic Resonance (CMR) imaging, which is the reference diagnostic method in this setting. METHODS: Fourteen CMR-defined acute myocarditis patients had a first 15-minutes ECG-triggered 68Ga-DOTATOC PET recording, 4.4 ± 3.0 days from peak troponin, and 10 had a second 4.3 ± 0.3 months later. Myocardial/blood SUVmax ratio was analyzed relative to the normal upper limit of 2.18, which had been previously determined from oncology 68Ga-DOTATOC-PET recordings of patients with a similar age range as the myocarditis patients. RESULTS: An increased myocardial 68Ga-DOTATOC uptake relative to blood activity was invariably observed during the acute phase. SUVmax ratio exceeded 2.18 in all patients during the acute phase but also in 3/10 patients at 4-months, at a time when there were no more signs of active inflammation on CMR. A residual myocardial 68Ga-DOTATOC uptake was still observed on all gated-PET cine loops at 4-months. CONCLUSION: These preliminary results suggest that 68Ga-DOTATOC ECG-triggered digital-PET may be as sensitive as CMR at detecting myocarditis during the acute phase and more sensitive at later stages.

Assessment of the routine reporting of very low-dose exercise-first myocardial perfusion SPECT from a large-scale real-world cohort and correlation with the subsequent reporting of coronary stenosis at angiography.

PURPOSE: Our study assesses the routine reporting of exercise ischemia using very low-dose exercise-first myocardial perfusion SPECT in a large number of patients and under real-life conditions, by evaluating correlations with the subsequent routine reporting of coronary stenosis by angiography and with factors that predict ischemia. METHODS: Data from 13,126 routine exercise MPI reports, from 11,952 patients (31% women), using very low doses of sestamibi and a high-sensitivity cardiac CZT camera, were extracted to assess the reporting of significant MPI-ischemia (> 1 left ventricular segment), to determine the MPI normalcy rate in a group with < 5% pretest probability of coronary artery disease (CAD) (n = 378), and to assess the ability of MPI to predict a > 50% coronary stenosis in patients with available coronary angiography reports in the 3 months after the MPI (n = 713). RESULTS: The median effective patient dose was 2.51 [IQR: 1.00-4.71] mSv. The normalcy rate was 98%, and the MPI-ischemia rate was independently predicted by a known CAD, the male gender, obesity, and a < 50% LV ejection fraction, ranging from 29.5% with all these risk factors represented to 1.5% when there were no risk factors. A > 50% coronary stenosis was significantly predicted by MPI-ischemia, less significantly for mild (odds ratio [95% confidence interval]: 1.61 [1.26-1.96]) than for moderate-to-severe MPI-ischemia (4.05 [3.53-4.57]) and was also impacted by having a known CAD (2.17 [1.83-2.51]), by a submaximal exercise test (1.48 [1.15-1.81]) and being ≥ 65 years of age (1.43 [1.11-1.76]). CONCLUSION: Ischemia detected using a very low-dose exercise-first MPI protocol in a large-scale clinical cohort and under real-life routine conditions is a highly significant predictor for the subsequent reporting of coronary stenosis, although this prediction is enhanced by other variables. This weakly irradiating approach is amenable to being repeated at shorter time intervals, in target patient groups with a high probability of MPI-ischemia.

The detection of infectious endocarditis may be enhanced by a repeat FDG-PET while maintaining patients on a ketogenic diet.

BACKGROUND: This study aims to determine whether the suppression of myocardial FDG uptake and detection of infectious endocarditis (IE) may be enhanced when FDG-PET is repeated on the next day while maintaining patients on a ketogenic diet in the interim. METHODS: Seventeen patients with definite IE underwent FDG-PET investigations both after a conventional metabolic preparation (> 12-hour fast after a low-carbohydrate evening meal) and a subsequent 12-hour extension of the low-carbohydrate diet followed by an additional > 12-hour fast. RESULTS: Plasma biomarkers showed increased ketogenic metabolism between the two FDG-PET scans. A myocardial FDG uptake persisted on the 1st PET in 9 patients (53%) for whom myocardial FDG uptake decreased significantly on the 2nd PET (SUVmax: 6.05 ± 3.25 vs 4.32 ± 3.47, P = 0.021), resulting in an enhancement in the diagnostic confidence of IE in 6 cases. These enhancements were not documented in the 8 patients exhibiting a total suppression of myocardial FDG uptake on the 1st PET. CONCLUSIONS: Better suppression of myocardial uptake and enhanced detection of IE may be achieved when an FDG-PET, showing an incomplete suppression of the myocardial FDG uptake, is repeated as soon as the next day, while maintaining patients on a ketogenic diet in the interim.

CT abnormalities evocative of lung infection are associated with lower 18F-FDG uptake in confirmed COVID-19 patients.

PURPOSE: CT signs that are evocative of lung COVID-19 infections have been extensively described, whereas 18F-FDG-PET signs have not. Our current study aimed to identify specific COVID-19 18F-FDG-PET signs in patients that were (i) suspected to have a lung infection based on 18F-FDG-PET/CT recorded during the COVID-19 outbreak and (ii) whose COVID-19 diagnosis was definitely established or excluded by appropriate viral testing. METHODS: Twenty-two consecutive patients referred for routine 18F-FDG-PET/CT examinations during the COVID-19 outbreak (March 25th to May 15th 2020) and for whom CT slices were evocative of a lung infection were included in the study. All patients had undergone a SARS-COV-2 diagnostic test to confirm COVID-19 infection (positivity was based on molecular and/or serological tests) or exclude it (negativity of at least the serological test). RESULTS: Eleven patients were confirmed to be affected by COVID-19 (COVID+), whereas the other eleven patients were not (COVID-) and were predominantly suspected of having bacterial pneumonia. CT abnormalities were not significantly different between COVID+ and COVID- groups, although trends toward larger CT abnormalities (p = 0.16) and lower rates of consolidation patterns (0.09) were observed in the COVID+ group. The maximal standardized uptake values (SUVmax) of lung areas with CT abnormalities were however significantly lower in the COVID+ than the COVID- group (3.7 ± 1.9 vs. 6.9 ± 4.1, p = 0.03), with the highest SUVmax consistently not associated with COVID-19. CONCLUSION: Among CT abnormalities evocative of lung infection, those related to COVID-19 are associated with a more limited 18F-FDG uptake. This observation may help improve our ability to detect COVID-19 patients.

Hypermetabolism of the spleen or bone marrow is an additional albeit indirect sign of infective endocarditis at FDG-PET.

PURPOSE: This study aimed at determining the diagnostic implications of indirect signs of infection at FDG-PET-i.e., hypermetabolisms of the spleen and/or bone marrow (HSBM)-when documented in patients with known or suspected infective endocarditis (IE). METHODS: HSBM were defined by higher mean standardized uptake values comparatively to that of the liver on FDG-PET images from patients with a high likelihood of IE and prospectively included in a multicenter study. RESULTS: Among the 129 included patients, IE was ultimately deemed as definite in 88 cases. HSBM was a predictor of definite IE (P = 0.014; odds ratio (OR) 3.2), independently of the criterion of an abnormal cardiac FDG uptake (P = 0.0007; OR 9.68), and a definite IE was documented in 97% (29/30) of patients showing both HSBM and abnormal cardiac uptake, 78% (7/9) of patients with only abnormal cardiac uptake, 67% (42/63) of patients with only HSBM, and 37% (10/27) of patients with neither one. CONCLUSION: In this cohort with a high likelihood of IE, HSBM is an additional albeit indirect sign of IE, independently of the criterion of an abnormal cardiac uptake, and could reinforce the suspicion of IE in the absence of any other infectious, inflammatory, or malignant disease.

177Lu-PSMA Treatment Monitoring Through Serial Fast Whole-Body Tomoscintigraphies Recorded With a Latest-Generation CZT-Camera.

ABSTRACT: The tomoscintigraphy monitoring of 177Lu-prostate-specific membrane antigen (PSMA) treatment may be helpful for quality control and predicting therapeutic response. Furthermore, the drawbacks of relatively low image quality and extended recording times can be overcome by new CZT-cameras providing fast, high-quality, whole-body recordings. Although still requiring further larger-scale confirmation, the current case report demonstrates that these CZT-cameras have the potential to provide straightforward and comprehensive 177Lu-PSMA treatment monitoring, that is, <20-minute whole-body tomoscintigraphy recording, tumor activities concordant with those from 68Ga-PSMA PET, and no requirement for any additional tracer injection.

Early 18F-FDG PET Flare-up Phenomenon After CAR T-Cell Therapy in Lymphoma.

ABSTRACT: 18F-FDG PET/CT imaging series were acquired on a 64-year-old woman with refractory diffuse large B lymphoma to monitor chimeric antigen receptor (CAR) T-cell therapy. Because of a clinical deterioration, 18F-FDG PET/CT performed 8 days after CAR T-cell therapy suggested an early flare-up phenomenon with new lymph node involvement, lymph node progression while a decrease in metabolic tumor volume. The 18F-FDG PET/CT 1 month after CAR T-cell therapy confirmed this hypothesis. Pseudoprogression in solid tumors treated by immunotherapy has generally been reported later after treatment.

Value of 68Ga-DOTATOC and Carbidopa-Assisted 18F-DOPA PET/CT for Insulinoma Localization.

Our objective was to assess the value of 68Ga-DOTATOC and carbidopa-assisted 18F-fluorodihydroxyphenylalanine (18F-DOPA) in 21 hypoglycemic patients. Methods: All patients who underwent 68Ga-DOTATOC or carbidopa-assisted 18F-DOPA PET/CT for suspicion of insulinoma from January 2019 to January 2021 were retrospectively analyzed. A final diagnosis of insulinoma was determined by pathologic reports or consensus. Results: During the study period, 21 patients underwent both 68Ga-DOTATOC and 18F-DOPA PET/CT. A final diagnosis of insulin-secreting tumor was reached in 12 cases, including 11 insulinomas and 1 small mixed neuroendocrine/nonneuroendocrine neoplasm. 18F-DOPA and 68Ga-DOTATOC PET/CT were positive in 5 (45%) and 7 (64%) of 11 cases, respectively, with 4 concordant positive findings. Moreover, 1 insulinoma was visualized exclusively by 18F-DOPA PET/CT and 3 by 68Ga-DOTATOC PET/CT only. 18F-DOPA and 68Ga-DOTATOC PET/CT were falsely positive in 1 nonfunctioning pancreatic neuroendocrine tumor. Conclusion: When 68Ga-exendin-4 is not available, 68Ga-somatostatin receptor PET/CT should be the first choice for insulinoma functional imaging.

Prospective Paired Comparison of 123I-FP-CIT SPECT Images Obtained With a 360°-CZT and a Conventional Camera.

PURPOSE: This study aimed to compare 123I-FP-CIT SPECT imaging obtained from a 360° cadmium-zinc-telluride (CZT) camera with different focus configurations and from a conventional Anger camera. METHODS: This prospective study (NCT03980418) included patients referred to 123I-FP-CIT SPECT imaging who consecutively underwent a 30-minute acquisition on a conventional camera immediately followed by two 15-minute acquisitions on the 360°-CZT camera with, respectively, striatum and brain focus and reconstruction parameters to give equivalent contrast ratios, albeit with higher spatial resolution for the CZT camera. Tomographic count sensitivities were calculated. The images were analyzed through visual, according to 5 independent physicians, and automatic semiquantitative analyses. RESULTS: Ninety-two patients were included in this study. The 360°-CZT camera tomographic count sensitivities showed increases of +25% and +18% for striatum and brain focus, respectively, as well as significantly higher quality scores (P ≤ 0.04) in comparison to the conventional camera. The κ scores of consensual visual analysis were 0.80 and 0.85, and correlation coefficients of semiquantitative analysis for striatum uptakes were 0.75 and 0.76 for the comparisons of images obtained with the 2 cameras, with striatum and brain focus, respectively, for the CZT camera. Advanced age was the single predictor of discordant cases (10/92 [11%]) showing systematically abnormal scans with the conventional camera, potentially as a result of partial volume effect. CONCLUSIONS: Irrespective of focus mode, this high-sensitivity 360°-CZT camera provides concordant 123I-FP-CIT SPECT results when compared with a conventional camera, but with shorter acquisition times, higher image quality, and few discordant cases possibly explained by its higher spatial resolution.

18F-DOPA PET/CT at the Forefront of Initial or Presurgical Evaluation of Small-Intestine Neuroendocrine Tumors.

Our objective was to compare the respective value of 68Ga-DOTATOC and 18F-DOPA PET/CT for initial staging or presurgical work-up of patients with small-intestine neuroendocrine tumors (SiNETs). Methods: This was a retrospective, multicenter, noninterventional investigation involving 53 non-surgically treated SiNET patients who underwent both 68Ga-DOTATOC and 18F-DOPA PET/CT within a 6-mo interval without surgical intervention or therapeutic change between the 2 PET/CT studies. Percentage detection rate was calculated according to per-region and per-lesion analyses. Sensitivity for primary tumor detection was assessed in 37 surgically treated patients, taking surgical results (76 SiNETs) as the diagnostic gold standard. Results: 68Ga-DOTATOC PET/CT and 18F-DOPA PET/CT individually identified at least 1 primary SiNET in 92% (34/37) of the patients. Intestinal tumor multifocality was confirmed by histology in 8 patients. 68Ga-DOTATOC and 18F-DOPA PET/CT were concordantly positive for tumor multifocality in 5 patients, discordantly positive in 2 patients, and concordantly negative in 1 patient. The detection rate for subdiaphragmatic nodal metastases on per-region-based analysis was 91% and 98% for 68Ga-DOTATOC and 18F-DOPA PET/CT, respectively (P = 0.18). 18F-DOPA PET/CT detected a higher number of abnormal subdiaphragmatic nodes (P = 0.009). Regarding mesenteric nodes only, 18F-DOPA PET/CT detected more positive regions (P = 0.005) and nodal lesions (P = 0.003) than 68Ga-DOTATOC PET/CT, including nodes at the origin of mesenteric vessels. For detection of distant metastases, 68Ga-DOTATOC and 18F-DOPA PET/CT performed equally well on a per-region-based analysis. As compared with 68Ga-DOTATOC, 18F-DOPA PET/CT detected more hepatic (P < 0.001), peritoneal (P < 0.001), and lung metastases (P < 0.001). Conclusion: 18F-DOPA PET/CT detected more lesions than 68Ga-DOTATOC PET/CT in the studied patients. The respective roles of the two should be discussed in terms of disease staging and treatment selection.

Feasibility of 177Lu Therapy Monitoring Using Fast Whole-Body SPECT Recordings Provided by a High-Speed 360° CZT Camera.

The whole-body absolute quantification of Lu-DOTATATE therapy was achieved using a high-speed 360° CZT SPECT/CT system. Twelve high-resolution swelling detectors may be positioned close to patients, providing a high-count sensitivity that is particularly advantageous for the low-count rate conditions of Lu imaging. After initially validating Lu quantification on phantom, serial whole-body SPECT/CT acquisitions of only 20 minutes were obtained for a 70-year-old woman treated by Lu-DOTATATE injections for a metastatic recurrence of a pancreatic neuroendocrine tumor. The progressive decrease in tumor uptake between the consecutive Lu-DOTATATE injections could be quantified, and thereby the corresponding dosimetry changes could be estimated.