177Lu-labeled somatostatin receptor targeted radionuclide therapy dosimetry in meningioma: a systematic review.

INTRODUCTION: Few therapeutic options are currently available for refractory meningiomas. Encouraging results have been reported for 177Lu-labeled somatostatin receptor-targeted radiopeptide therapy (SSTR-RT). The current therapeutic scheme is based on the fixed doses that are recommended for neuroendocrine tumor treatment. However, in personalized medicine, tumor dosimetry can be determined from repeat 177Lu scintigraphy. The aim of this review was to report on the methods used for calculating the tumor absorbed dose (AD) in meningioma patients treated with 177Lu-SSTR-RT and their values. EVIDENCE ACQUISITION: The search was performed in Medline, Embase and the Cochrane Library until March 1st, 2024 to retrieve papers related to the topic. The following terms were used for searching: (meningioma) AND ((sstr) OR (receptors somatostatin) OR (somatostatin) OR (octreotide)) AND ((PRRT) OR (radionuclide therapy) OR (dotatate) OR (dotatoc) OR (177Lu-DOTATOC) OR (177Lu-DOTATATE) OR (radiopeptide)). EVIDENCE SYNTHESIS: Seven articles (including 46 patients and 108 cycles of treatment) reporting on tumor AD during 177Lu-SSTR-RT were included in the analysis. The methods of acquisition, reconstruction parameters and postimage processing to determine tumor AD were very heterogeneous among the studies. The meningioma AD associated with the agonist 177Lu-SSTR-RT reported in the majority of studies ranged from 0.1-1.5 Gy/GBq, which was lower than that reported for neuroendocrine tumors (1.3-22.9 Gy/GBq). CONCLUSIONS: The tumor AD that was reported during treatment with 177Lu-SSTR-RT in refractory meningioma patients is generally low. Harmonization of the methodology for dosimetry calculations is needed to compare the different reported values and optimize treatment at the individual level.

Factors Associated with Myocardial Uptake on Oncologic Somatostatin PET Investigations and Differentiation from Myocardial Uptake of Acute Myocarditis.

Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. Methods: We analyzed factors associated with the detection of myocardial [68Ga]Ga-DOTATOC uptake in 508 [68Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [68Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. Results: Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(ß), 0.805; 95% CI, 0.728-0.890; P < 0.001) and age (exp(ß), 1.005; 95% CI, 1.001-1.009; P = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUVmax ratio using somatostatin analog treatment (P < 0.001) and history of coronary artery disease (P = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUVmax ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm3 provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). Conclusion: Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.

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.

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.

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.

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.

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.

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.