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  • 1
    Online Resource
    Online Resource
    Preclinical evaluation of targeted therapies in Sdhb-mutated tumors
    Bioscientifica ; 2022
    In:  Endocrine-Related Cancer Vol. 29, No. 6 ( 2022-06-01), p. 375-388
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 29, No. 6 ( 2022-06-01), p. 375-388
    Abstract: Therapies for metastatic SDHB -dependent pheochromocytoma and paraganglioma (PPGL) are limited and poorly efficient. New targeted therapies and identification of early non-invasive biomarkers of response are thus urgently needed for these patients. We characterized an in vivo allograft model of spontaneously immortalized murine chromaffin cells (imCC) with inactivation of the Sdhb gene by dynamic contrast-enhanced MRI (DCE-MRI) and 18 FDG-PET. We evaluated the response to several therapies: IACS-010759 (mitochondrial respiratory chain complex I inhibitor), sunitinib (tyrosine kinase inhibitor with anti-angiogenic activity), talazoparib (poly ADP ribose polymerase (PARP) inhibitor) combined or not to temozolomide (alkylating agent), pharmacological inhibitors of HIF2a (PT2385 and PT2977 (belzutifan)) and molecular inactivation of HIF2a (imCC Sdhb −/− shHIF2a). Multimodal imaging was performed, including magnetic resonance spectroscopy ( 1 H-MRS) to monitor the level of succinate in vivo . The allografted model of Sdhb −/− imCC reflected SDHB-deficient tumors, with increased angiogenesis and a particular avidity for 18 FDG. After 14 days of treatment, IACS-010759, sunitinib and talazoparib at high doses allowed a significant reduction of the tumor volumes. In contrast to the tumor growth inhibition observed in Sdhb −/− shHIF2a imCC tumors, pharmacological inhibitors of HIF2a (PT2385 and belzutifan) showed no antitumor action in this model, alone or in combination with sunitinib. 1 H-MRS, but not DCE-MRI, enabled the monitoring response to sunitinib, which was the best treatment in this study, promoting a decrease in succinate levels detected in vivo . This study paves the way for new therapeutic options and reveals a potential new early biomarker of response to treatment in SDHB -dependent PPGL.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-22-0030
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2022
    detail.hit.zdb_id: 2010895-3
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  • 2
    Online Resource
    Online Resource
    Optic Nerve Sheath Meningiomas: Solving Diagnostic Challenges with 68Ga-DOTATOC PET/CT
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 13 ( 2023-07-07), p. 2307-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 13 ( 2023-07-07), p. 2307-
    Abstract: 68Ga-DOTATOC PET could be a noninvasive, highly sensitive, and specific technique for the challenging diagnosis of optic nerve sheath meningioma (ONSM). Our objective was to report the use and results of 68Ga-DOTATOC PET in suspected ONSM. Twelve subjects who underwent 68Ga-DOTATOC PET for suspected ONSM in our department were retrospectively included. Standardised clinical and radiological data were collected. The PET examination results were classified as positive or negative, and lesion standardised uptake values (SUVmax) were recorded. 68Ga-DOTATOC PET confirmed positive uptake in six cases (SUVmax 〉 5), leading to ONSM diagnoses followed by radiation therapy in patients with vision loss. Six 68Ga-DOTATOC PET scans were considered negative (SUVmax 〈 5); these comprised one case of neurosarcoidosis, one cavernous malformation, and four uncertain diagnoses, leading to further investigation. 68Ga-DOTATOC PET was helpful in tumour volume delineation before radiation therapy, leading to a decrease in dose exposure. Noninvasive 68Ga-DOTATOC PET should be performed before treating nonhistologically proven meningiomas with radiotherapy or stereotactic radiosurgery, particularly in cases of uncertain diagnosis with MRI, which characterises most ONSM cases. PET SUVmax thresholds to distinguish meningioma from nonspecific uptake in other lesions need to be adapted to ONSM. 68Ga-DOTATOC PET improves the intraorbital lesion diagnostic approach and therefore impacts therapeutic management.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13132307
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662336-5
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  • 3
    Online Resource
    Online Resource
    High 18F-FDOPA PET Uptake in Primary Central Nervous System Lymphoma
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Clinical Nuclear Medicine Vol. 46, No. 1 ( 2021-1), p. e59-e60
    Details
    In: Clinical Nuclear Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 1 ( 2021-1), p. e59-e60
    Abstract: We present a 42-year-old woman with primary central nervous system lymphoma (PCNSL) and strong 18 F-FDOPA PET uptake. 18 F-FDOPA PET has high diagnostic accuracy in gliomas and brain metastases. The l -type amino acid transporter 1, targeted by 18 F-FDOPA and 11 C-MET PET, is a cell-type transporter usually upregulated in malignant tumors, including PCNSL. In this line, strong uptake was already shown with 11 C-MET in PCNSL. We report the same findings with 18 F-FDOPA. Consequently, PCNSL is a possible differential neoplastic diagnosis of 18 F-FDOPA uptake among neoplastic lesions.
    Type of Medium: Online Resource
    ISSN: 1536-0229 , 0363-9762
    URL: Article
    DOI: 10.1097/RLU.0000000000003303
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2045053-9
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  • 4
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    Online Resource
    Somatostatin Receptor Theranostics for Refractory Meningiomas
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 8 ( 2022-08-04), p. 5550-5565
    Details
    In: Current Oncology, MDPI AG, Vol. 29, No. 8 ( 2022-08-04), p. 5550-5565
    Abstract: Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas (n = 29); 57.1% for WHO grade II (n = 21); and 0 % for WHO grade III (n = 12). For all grades (n = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol29080438
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 5
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    Online Resource
    SDHx mutation and pituitary adenoma: can in vivo 1H-MR spectroscopy unravel the link?
    Bioscientifica ; 2023
    In:  Endocrine-Related Cancer Vol. 30, No. 2 ( 2023-02-01)
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 30, No. 2 ( 2023-02-01)
    Abstract: Germline mutations in genes encoding succinate dehydrogenase (SDH) are frequently involved in pheochromocytoma/paraganglioma (PPGL) development and were implicated in patients with the ‘3PAs’ syndrome (associating pituitary adenoma (PA) and PPGL) or isolated PA. However, the causality link between SDHx mutation and PA remains difficult to establish, and in vivo tools for detecting hallmarks of SDH deficiency are scarce. Proton magnetic resonance spectroscopy ( 1 H-MRS) can detect succinate in vivo as a biomarker of SDHx mutations in PGL. The objective of this study was to demonstrate the causality link between PA and SDH deficiency in vivo using 1 H-MRS as a novel noninvasive tool for succinate detection in PA. Three SDHx -mutated patients suffering from a PPGL and a macroprolactinoma and one patient with an apparently sporadic non-functioning pituitary macroadenoma underwent MRI examination at 3 T. An optimized 1 H-MRS semi-LASER sequence (TR = 2500 ms, TE = 144 ms) was employed for the detection of succinate in vivo. Succinate and choline-containing compounds were identified in the MR spectra as single resonances at 2.44 and 3.2 ppm, respectively. Choline compounds were detected in all the tumors (three PGL and four PAs), while a succinate peak was only observed in the three macroprolactinomas and the three PGL of SDHx -mutated patients, demonstrating SDH deficiency in these tumors. In conclusion, the detection of succinate by 1 H-MRS as a hallmark of SDH deficiency in vivo is feasible in PA, laying the groundwork for a better understanding of the biological link between SDHx mutations and the development of these tumors.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-22-0198
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2023
    detail.hit.zdb_id: 2010895-3
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  • 6
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    Online Resource
    Risk stratification of adrenal masses by [ 18 F]FDG PET/CT: Changing tactics
    Wiley ; 2021
    In:  Clinical Endocrinology Vol. 94, No. 2 ( 2021-02), p. 133-140
    Details
    In: Clinical Endocrinology, Wiley, Vol. 94, No. 2 ( 2021-02), p. 133-140
    Abstract: [ 18 F]FDG PET/CT improves adrenal tumour characterization. However, there is still no consensus regarding the optimal imaging biomarkers of malignancy. Objectives To assess the performance of Tumour standardized uptake value (SUV) max :Liver SUV max for malignancy‐risk and to build and evaluate a prediction model. Design/Methods The cohort consisted of consecutive patients with adrenal masses evaluated by [ 18 F]FDG PET/CT. The gold standard for malignancy was based on histology or a multidisciplinary consensus in nonoperated cases. The performance of the previously reported cut‐off for Tumour SUV max :Liver SUV max ( 〉 1.5) was evaluated in this independent cohort. Additionally, a predictive model of malignancy was built from the training cohort (previous study) and evaluated in the validation cohort (current study). Results Sixty‐four patients were evaluated; 28% of them had a Cushing's syndrome. Fifty‐four adrenal masses were classified as benign and 10 as malignant (including 7 adrenocortical carcinomas). Compared to benign masses, malignant lesions were larger in size, had higher unenhanced densities and higher [ 18 F]FDG uptake. CT‐derived anthropometric parameters did not differ between benign and malignant masses. A tumour SUV max :Liver SUV max   〉  1.5 showed a good diagnostic performance: Se = 90.0%/Sp = 92.6%/PPV = 69.2%/NPV = 98.0% and accuracy = 92.2%. A predictive model based on tumour size and tumour‐to‐liver uptake SUV max ratio for malignancy‐risk was validated and provides a complementary approach to the ratio. Conclusions Tumour SUV max :Liver SUV max uptake ratio is a useful biomarker for diagnosis of adrenal masses. Another tactic would be to calculate with the model an individual risk of malignancy and integrate this information into a shared decision‐making process.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    URL: Article
    DOI: 10.1111/cen.v94.2
    DOI: 10.1111/cen.14338
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2004597-9
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