Al18F-NOTA-Octreotide PET/CT and 18F-FDG PET/CT for Detecting Cerebellar Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.

ABSTRACT: Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.

Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE: Nursing Roles in Managing Patients With Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a diverse family of cancers that occur within the gastrointestinal tract and pancreas. Peptide receptor radionuclide therapy (PRRT) via 177Lu-DOTATATE is a newer therapeutic option for certain patients with somatostatin receptor-positive GEP-NETs. OBJECTIVES: This review informs on how oncology nurses treating patients with GEP-NETs receiving PRRT using 177Lu-DOTATATE can facilitate care. METHODS: Guidance on the monitoring, management, and care of patients undergoing PRRT for GEP-NETs was developed based on published literature and the nursing experience of the authors. A case study is summarized to highlight key concepts. FINDINGS: Oncology nurses provide assessment, education, direct care, and emotional support when caring for patients with GEP-NETs receiving PRRT with 177Lu-DOTATATE. As the treatment landscape evolves, so too will these roles and responsibilities.

Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma.

PURPOSE: There are no effective medical therapies for patients with meningioma who progress beyond surgical and radiotherapeutic interventions. Somatostatin receptor type 2 (SSTR2) represents a promising treatment target in meningiomas. In this multicenter, single-arm phase II clinical study (NCT03971461), the SSTR2-targeting radiopharmaceutical 177Lu-DOTATATE is evaluated for its feasibility, safety, and therapeutic efficacy in these patients. PATIENTS AND METHODS: Adult patients with progressive intracranial meningiomas received 177Lu-DOTATATE at a dose of 7.4 GBq (200 mCi) every eight weeks for four cycles. 68Ga-DOTATATE PET-MRI was performed before and six months after the start of the treatment. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Secondary endpoints were safety and tolerability, overall survival (OS) at 12 months (OS-12), median PFS, and median OS. RESULTS: Fourteen patients (female = 11, male = 3) with progressive meningiomas (WHO 1 = 3, 2 = 10, 3 = 1) were enrolled. Median age was 63.1 (range 49.7-78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Seven patients (50%) achieved PFS-6. Best radiographic response by modified Macdonald criteria was stable disease (SD) in all seven patients. A >25% reduction in 68Ga-DOTATATE uptake (PET) was observed in five meningiomas and two patients. In one lesion, this corresponded to >50% reduction in bidirectional tumor measurements (MRI). CONCLUSIONS: Treatment with 177Lu-DOTATATE was well tolerated. The predefined PFS-6 threshold was met in this interim analysis, thereby allowing this multicenter clinical trial to continue enrollment. 68Ga-DOTATATE PET may be a useful imaging biomarker to assess therapeutic outcome in patients with meningioma.

Fibromatosis mimicking relapse of a neuroendocrine tumor at 68Ga-DOTATOC positron-emission tomography/computed tomography.

Mesenteric fibromatosis (desmoid tumor) is a locally aggressive fibroblastic lesion, characterized by a high recurrence rate that makes treatment challenging. Currently, there is no evidence-based treatment approach. We report the case of a female patient with a history of neuroendocrine tumor, who underwent 68Ga-DOTATOC positron-emission tomography/computed tomography (PET/CT), showing increased focal abdominal uptake suggestive of disease relapse. Histological examination revealed typical findings of fibromatosis. These findings indicate the expression of staining for somatostatin receptors (SSTRs) on fibromatosis cell surface and suggest to include fibromatosis among the potential causes of false-positive results at 68Ga PET/CT. Moreover, SSTRs expressed in desmoid tumors could be further investigated as a therapeutic target.

[68Ga-DOTATOC PET/CT for Diagnosing Neuroendocrine Tumors].

Lutathera is a peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and was approved as the first PRRT drug in Japan in 2021. Although neuroendocrine tumors are often less aggressive than other highly malignant and invasive tumors, there have been few effective therapy options, so "Lutathera"is a long-awaited treatment. Lutathera is indicated for the treatment of "somatostatin receptor-positive neuroendocrine tumors". Currently, in Japan, the only imaging method to evaluate the expression of somatostatin receptors in lesions is scintigraphy using In-111 pentetreotide(OctreoScan). In this section, we would like to introduce the current status of the 68Ga-DOTA-SSA PET/CT using somatostatin analogue(SSA)in our institution.

[Theranostics for Well and Moderately Differentiated GEP-NEN]. / Theranostics bei gut bis mäßig differenzierten GEP-NEN.

Neuroendocrine neoplasms (NEN) are rare, heterogeneous, and typically slowly growing tumours. The most common location is the gastro-entero-pancreatic system (GEP-NEN). NENs are classified according to their proliferative activity (Ki-67 index, G1-3). In this context, well-differentiated tumours typically express somatostatin receptors (SSTR), thus serving as targets for nuclear medicine theranostics. In this approach, diagnostic molecular imaging, usually by positron emission tomography/computed tomography (PET/CT), can be followed by individually tailored peptide radioreceptor therapy (PRRT) with a ß-emitter labeled radiopharmaceutical. In meta-analyses, diagnostics using SSTR-directed PET/CT showed a sensitivity of 93% and a specificity of 96%. SSTR-directed diagnostics can also be used to trace tumours in-vivo, enabling radioguided surgery. The decision to initiate PRRT should always be made in an interdisciplinary tumour conference and tumour progression during previous therapy should be documented. This treatment is administered intravenously for 4 times at 8-week intervals in specialised nuclear medicine centres. PRRT efficacy was prospectively evaluated in the NETTER-1 study and demonstrated a significant improvement in progression-free survival (primary endpoint). Based on these results, Lutathera (177Lu-DOTATATE) is now available as a radiopharmaceutical approved in Germany for the treatment of non-resectable or metastatic or progressive, well-differentiated (G1 and G2), SSTR-positive GEP-NEN.

Metastasis From Clear Cell Renal Cell Carcinoma Mimicking Well-Differentiated Pancreatic Neuroendocrine Tumor at 18F-FDG and 68Ga-DOTATOC PET/CT.

ABSTRACT: Dual-tracer PET/CT with both 18F-FDG and 68Ga-DOTA-conjugated peptides is currently used in clinical routine for characterizing pNET (pancreatic masses suspicious for neuroendocrine tumor). We describe here the case of a 81-year-old man with a pancreatic lesion showing high 68Ga-DOTATOC uptake and mild 18F-FDG avidity, thus suggesting a well-differentiated pNET, which resulted at endoscopic ultrasound-guided fine-needle aspiration to be a clear cell renal cell carcinoma metastasis. In fact, the patient had right nephrectomy for clear cell renal cell carcinoma 27 years earlier. This case puts light on the role of PET/CT with 68Ga-DOTATOC in imaging RCC, a field which deserves to be further explored.

Rechallenge With Additional Doses of 177 Lu-DOTATOC After Failure of Maintenance Therapy With Cold Somatostatin Analogs.

ABSTRACT: Here, we report a case of a 52-year-old woman with a well-differentiated, metastasized neuroendocrine tumor (NET G1) of the duodenum. Initial imaging with 68 Ga-DOTATOC revealed multiple sites of disease with intense uptake. Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATOC induced partial remission. Treatment was then switched to cold somatostatin analog as a maintenance therapy. After 2 years of follow-up, progressive disease with multiple lesions in the skeleton was noted. Given the initial response to PRRT, a rechallenge with another 2 cycles of PRRT were given, and the patient had an excellent response to treatment, in particular in the skeleton.

Heterogeneity of SSTR2 Expression Assessed by 68Ga-DOTATOC PET/CT Using Coefficient of Variation in Patients with Neuroendocrine Tumors.

High levels of somatostatin receptor subtype 2 (SSTR2) are a prerequisite for therapy with unlabeled or labeled somatostatin analogs. However, it is still unclear how the heterogeneity of SSTR2 expression may affect tumor response to therapy. The aim of our study was to test the ability of an imaging parameter such as coefficient of variation (CoV) derived from PET/CT with 68Ga-peptides in the evaluation and quantification of the heterogeneity of SSTR2 expression within primary and metastatic lesions of patients with neuroendocrine tumors. Methods: Thirty-eight patients with pathologically proven neuroendocrine tumors who underwent 68Ga-DOTATOC PET/CT were studied. Primary tumors were localized in the gastroenteropancreatic, bronchopulmonary, and other anatomic districts in 25, 7, and 6 patients, respectively. Malignant lesions were segmented using an automated contouring program and an SUV threshold of more than 2.5 or, in the case of liver lesions, a threshold of 30% of the SUVmax The imaging parameters SUVmean, CoV, SUVmax, receptor-expressing tumor volume, and total lesion receptor expression were obtained for each lesion. SUVmean, CoV, and SUVmax were also obtained for representative volumes of normal liver and spleen, as well as for the whole pituitary gland. Results: In total, 107 lesions were analyzed, including 35 primary tumors, 32 metastatic lymph nodes, and 40 distant metastases. Average CoVs were 0.49 ± 0.20 for primary tumors, 0.57 ± 0.26 for lymph node metastases, and 0.44 ± 0.20 for distant metastases. The CoVs of malignant lesions were up to 4-fold higher than those of normal tissues (P ≤ 0.0001). Among malignant lesions, the highest CoV was found for bone metastases (0.68 ± 0.20), and it was significantly greater than that of primary lesions (P = 0.01) and liver metastases (P < 0.0001). On the other hand, the lowest CoV was found for liver lesions (0.32 ± 0.07), probably because of the high background uptake. Conclusion: Our findings indicate that the heterogeneity of uptake, reflecting that of SSTR2, varies with the type and site of malignant lesions as assessed by CoVs obtained from 68Ga-DOTATOC PET/CT scans. These observations may be related to different biologic characteristics of tumor lesions in the same patient-differences that may affect their response to treatment with both labeled and unlabeled somatostatin analogs.

Role of 68Ga-DOTATOC PET/CT in Insulinoma According to 3 Different Contexts: A Retrospective Study.

OBJECTIVE: The aim of this study was to assess the performance of 68Ga-DOTATOC PET/CT in the detection and extension of insulinomas according to 3 different contexts: sporadic benign, sporadic metastatic, and multiple endocrine neoplasia type 1 (MEN1). PATIENTS AND METHODS: The data of 71 adult patients who underwent 68Ga-DOTATOC PET/CT for suspected or confirmed sporadic insulinoma, suspicion of insulinoma in the context of MEN1, follow-up of metastatic insulinoma, or suspicion of recurrence of insulinoma were retrospectively analyzed. Pathological examination or strong clinical and biological findings were used as standards of truth. RESULTS: For the assessment of a confirmed sporadic insulinoma in 17 patients, the sensitivity of SR-PET was 75%, including 2 patients for whom metastatic lesions had been revealed by SR-PET. For 35 patients with a suspicion of insulinoma, the sensitivity was 39%. In 10 patients followed up for metastatic insulinoma, the sensitivity was 100%. For 5 patients with a history of MEN1, interpretation of SR-PET was difficult, as 3 of them presented with multiple pancreatic uptake foci. The global sensitivity of SR-PET in all insulinomas excluding those with a MEN1 story was 64% (100% for metastatic insulinomas, 62% for benign insulinomas), with a specificity of 89%. CONCLUSIONS: 68Ga-DOTATOC PET/CT is a useful examination tool for the assessment of insulinomas in selected contexts, with very high performance for the detection and extension workup of metastatic insulinomas and high specificity for the detection of sporadic benign insulinomas. The examination should be completed with GLP-1 receptor PET when it is negative or in a MEN1 context.

Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting.

ABSTRACT: Neuroendocrine tumors (NETs) are rare, but the incidence and prevalence of NETs are increasing in the United States. While surgery is the preferred treatment for NETs, it is not a viable option for metastatic disease. Lutathera (177Lu-DOTATATE) is approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of gastroenteropancreatic (GEP)-NETs in adults. There is limited information on GEP-NET treatment responses to Lutathera.Our institution launched a peptide receptor radionuclide therapy (PRRT) service line using Lutathera with involvement from a multidisciplinary team and complete collaboration between hospital administration and clinical providers. A prospective registry study was also established in order to collect patient demographics and clinical data regarding the treatment of GEP primary NETs with Lutathera.Between August 2018 and July 2020, 35 GEP-NET patients were treated with Lutathera, of which 65.71% received 4 complete cycles and 25.71% received 3 cycles; 5.71% and 2.86% received 2 and 1 cycles of PRRT, respectively. Most adverse events during the course of our study were low grade using the common terminology criteria for adverse events system. Of the patients who completed all 4 cycles: 22% showed partial response to Lutathera, 44% showed stable disease, and 13% showed disease progression based on a qualitative assessment of positron emission tomography/computed tomography imaging.From our experience, Lutathera was well tolerated in patients with GEP-NET. Additional studies are needed to examine long-term clinical and patient-reported outcomes associated with GEP-NET treatment as well as financial considerations for hospitals embarking on a PRRT program.

Optimized method for normal range estimation of standardized uptake values (SUVmax, SUVmean) in liver SPECT/CT images with somatostatin analog [99mTc]-HYNIC-TOC (Tektrotyd).

BACKGROUND: 99mTc-hydrazinonicotinyl-Tyr3-octreotide ([99mTc]-HYNIC-TOC [Tektrotyd]) is a radiopharmaceutical used for the diagnosis of lesions with overexpression of somatostatin receptors. The purpose of this study was to optimize the method and estimate normal ranges for standardized uptake values of Tektrotyd in healthy livers. MATERIAL AND METHODS: An analysis of standardized uptake value (SUVs) normal ranges was performed for images acquired in a selected "healthy group" of 42 patients evaluated for neuroendocrin tumors. The "pathological group" comprised 20 patients with liver lesions detected by scintigraphic imaging. Normal ranges for radiopharmaceutical uptake values were estimated based on the quantitative analysis of images acquired with a GE Healthcare NM/CT 850 gamma camera. RESULTS: The method for healthy liver segmentation in single photon emission computed tomography/computed tomography (SPECT/CT) was optimized. The normal range of SUVs for the liver was: standardized uptake value body weight (SUVbw) max [5.2-14.0] g/mL and standardized uptake value lean body mass (SUVlbm) [3.5-9.5] g/mL. The relative standard error (relative SE) of activity concentration estimated in the phantom study for the largest hot spheres was: ϕ = 37 mm - 5.9%, ϕ = 28 mm - 7.1%, ϕ = 22 mm - 11.4%, and ϕ = 17 mm - 22%. CONCLUSIONS: Segmentation in the mid-coronal computed tomography (CT) image, at one-fourth of the height of the liver measured from the top, with a medium-sized volume of interest (VOI) outlined on a given transverse SPECT slice was regarded as the optimal method for estimating normal ranges for standardized uptake values. It is necessary to standardize quantification methods in the SPECT/CT studies. Our work is a step forward in obtaining standardization of SPECT/CT SUV calculation methods. Calculations for radiopharmaceutical uptake in tumors with volumes smaller than 5 mL are biased with a significant measurement error.

68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine well-differentiated tumours.

PURPOSE: To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. METHODS: One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018-June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs' histopathological prognostic factors were evaluated using Spearman's coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters' predictive performance. RESULTS: Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). CONCLUSION: This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness.

Comparing Somatostatin Analogs in the Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: The 2 approved somatostatin analogs (SSAs) in the first-line treatment of advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are octreotide long-acting release (Sandostatin LAR) and somatuline depot (Lanreotide). The study's objective was to compare progression-free survival (PFS) and overall survival (OS) of patients (pts) with GEP-NETs treated with somatuline or octreotide LAR. Pts and Methods: Pts with advanced well-differentiated GEP-NET who received either SSA at Emory University between 1995 and 2019 were included after institutional review board approval. The primary end point was PFS, defined as time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.1, or clinical progression) or death. The secondary end point was OS. Kaplan-Meier curves were generated, and log-rank tests were conducted to compare the survival outcomes. RESULTS: A total of 105 pts were identified. The mean age was 62.1 years (SD ± 11.8). The male-to-female ratio was 51:54. The majority (N = 69, 65.7%) were white. Most pts had grade 2 (G2) disease (N = 44, 41.9%). Primary location was small bowel in 58 (55.2%), pancreas in 27 (25.7%), and other in 20 (19.0%). Functional tumors were defined in 32 pts distributed equally between the 2 groups. Distribution of treatment was similar in the 2 groups, with 54 receiving octreotide LAR and 51 receiving somatuline depot. The median PFS for the octreotide LAR and somatuline depot groups was 12 months (95% CI, 6-18 months) and 10.8 months (95% CI, 6-15.6 months), respectively, and the difference was not statistically significant (p = 0.2665). For pts with G1 disease, the median PFS for the octreotide LAR and somatuline depot was 8.4 versus 32.4 months, respectively, and the difference was not statistically significant (p = 0.159). For G2 disease, the difference in median PFS between octreotide LAR and somutaline depot groups was statistically significant (12 vs. 7.2 months, respectively; p = 0.0372). The mean follow-up time for octreotide LAR was 21.6 months versus 11.3 months for somatuline depot. CONCLUSIONS: Overall, there was no difference in PFS between octreotide LAR and somatuline depot for pts with well-differentiated, metastatic GEP-NETs. A prospective study is worth designing selecting for G.

External Validation of a Clinical Score for Patients With Neuroendocrine Tumors Under Consideration for Peptide Receptor Radionuclide Therapy.

Importance: Despite the benefit of peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs), no clinical metric to anticipate benefit from the therapy for individual patients has been previously defined. Objective: To assess whether the prognostic ability of the clinical score (CS) could be validated in an external cohort of patients with WD NETs. Design, Setting, and Participants: This multicenter cohort study's analysis included patients with WD NETs who were under consideration for peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate between March 1, 2016, and March 17, 2020. The original cohort included patients from Vanderbilt-Ingram Cancer Center. The validation cohort included patients from Ochsner Medical Center, Markey Cancer Center, and Rush Medical Center. Patients with paragangliomas, pheochromocytomas and neuroblastomas were excluded. Statistical analysis was performed from June to November 2021. Exposures: PRRT with 177Lu-dotatate or alternate therapies such as everolimus, sunitinib, or capecitabine plus temozolomide. Main Outcomes and Measures: The primary outcome was progression-free survival (PFS) and was estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusting for primary tumor site, tumor grade, and number of PRRT doses administered was used to analyze association between CS and outcomes. Results: A total of 126 patients (median age [IQR] age: 63.6 [52.9-70.7] years; 64 male individuals) were included in the validation cohort, and the combined cohort (validation and original cohorts combined) had a total of 248 patients (median [IQR] patient age: 63.3 [53.3-70.3] years; 126 male individuals). In the validation cohort, on multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.61; 95% CI, 1.64-4.16). After finding an association of the CS with PFS in the validation cohort, the original and validation cohorts were combined into the cohort for this analysis. On multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.52; 95% CI, 1.89-3.36). Conclusions and Relevance: Increases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort. These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from PRRT for patients with WD NETs and may be a clinical tool for patients being considered for PRRT.

Multiparametric 18F-FDG and 68GA-DOTATOC PET Imaging in Bone Metastatic Meningioma Before Radionuclide Therapy: Assessment of Tumor Heterogeneity.

ABSTRACT: This report presents the case of a 61-year-old woman with assessment of fronto-temporo-sphenoidal refractory meningioma before radionuclide therapy with pretherapeutic 68Ga-DOTATOC PET/CT. Given the discovery of osteolytic lesions, 18F-FDG PET/CT is planned to search for the primitive origin. Meningioma bone metastasis is confirmed with spine biopsies. The presence of dedifferentiated meningioma lesions indicating that high somatostatin receptor expression does not necessarily coincide with areas of increased glucose metabolism. 18F-FDG and 68Ga-DOTATOC PET/CT allows optimal characterization of tumor heterogeneity and guide targeted therapeutic management before PPRT.

Translating a radiolabeled imaging agent to the clinic.

Molecular Imaging is entering the most fruitful, exciting period in its history with many new agents under development, and several reaching the clinic in recent years. While it is unusual for just one laboratory to take an agent from initial discovery through to full clinical approval the steps along the way are important to understand for all interested participants even if one is not involved in the entire process. Here, we provide an overview of these processes beginning at discovery and preclinical validation of a new molecular imaging agent and using as an exemplar a low molecular weight disease-specific targeted positron emission tomography (PET) agent. Compared to standard drug development requirements, molecular imaging agents may benefit from a regulatory standpoint from their low mass administered doses, they nonetheless still need to go through a series of well-defined steps before they can be considered for Phase 1 human testing. After outlining the discovery and preclinical validation approaches, we will also discuss the nuances of Phase 1, Phase 2 and Phase 3 studies that may culminate in an FDA general use approval. Finally, some post-approval aspects of novel molecular imaging agents are considered.

Intracavernous Schwannoma Characterized With 18F-FDG, 68Ga-DOTATOC, and 18F-Choline PET.

ABSTRACT: We report the case of a 75-year-old man with history of prostate cancer whose left intracavernous lesion was successfully characterized by 3 PETs performed successively with different tracers. This poorly characterized tumor was initially discovered on an MRI conducted to investigate an acute diplopia and slowly growing during follow-up. On 18F-FDG PET, the lesion showed no significant uptake, and no extracranial lesion was found nor did it have increased 68Ga-DOTATOC uptake. Finally, this tumor displayed a high 18F-choline uptake, and no extracranial lesion was revealed with this tracer. The diagnosis of schwannoma without malignancy criterion was proven by biopsy.

Prognostic Value of Whole-Body PET Volumetric Parameters Extracted from 68Ga-DOTATOC PET/CT in Well-Differentiated Neuroendocrine Tumors.

Our objective was to evaluate the prognostic value of somatostatin receptor tumor burden on 68Ga-DOTATOC PET/CT in patients with well-differentiated (WD) neuroendocrine tumors (NETs). Methods: We retrospectively analyzed the 68Ga-DOTATOC PET/CT scans of 84 patients with histologically confirmed WD NETs (51 grade 1, 30 grade 2, and 3 grade 3). For each PET/CT scan, all 68Ga-DOTATOC-avid lesions were independently segmented by 2 operators using a customized threshold based on the healthy liver SUVmax (LIFEx, version 5.1). Somatostatin receptor-expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE = SRETV × SUVmean) were extracted for each lesion, and then whole-body SRETV and TLSRE (SRETVwb and TLSREwb, respectively) were defined as the sum of SRETV and TLSRE, respectively, for all segmented lesions in each patient. Time to progression (TTP) was defined as the combination of disease-free survival in patients undergoing curative surgery (n = 10) and progression-free survival for patients with unresectable or metastatic disease (n = 74). TTP and overall survival were calculated by Kaplan-Meier analysis, log-rank testing, and the Cox proportional-hazards regression model. Results: After a median follow-up of 15.5 mo, disease progression was confirmed in 35 patients (41.7%) and 14 patients died. A higher SRETVwb (>39.1 cm3) and TLSREwb (>306.8 g) correlated significantly with a shorter median TTP (12 mo vs. not reached; P < 0.001). In multivariate analysis, SRETVwb (P = 0.005) was the only independent predictor of TTP regardless of histopathologic grade and TNM staging. Conclusion: According to our results, SRETVwb and TLSREwb extracted from 68Ga-DOTATOC PET/CT could predict TTP or overall survival and might have important clinical utility in the management of patients with WD NETs.

Dosimetry of 177Lu-DOTATOC first circle treatment in patients with advanced metastatic neuroendocrine tumors: A pilot study in China.

First cycle dosimetry calculation of 177Lu-DOTATOC (single activity:1.59-3.49 GBq) was carried out in eight patients with advanced neuroendocrine tumors (NETs) who underwent whole-body planar (0.5, 24, 48, 72 h) and SPECT/CT scans (24 h). Focal uptake of 177Lu-DOTATOC was found in primary and metastatic tumors. Organs with the highest absorbed doses per injected activity were tumors (1.293 ± 0.862 mGy/MBq) and spleen (0.461 ± 0.408 mGy/MBq), while low absorbed doses were observed in kidneys (0.384 ± 0.112 mGy/MBq) and bone marrow (0.0297 ± 0.0123 mGy/MBq). 177Lu-DOTATOC is safe, well-tolerated and appropriate in Chinese NETs patients for PRRT.