scholarly journals Peptide Receptor Radionuclide Therapy for a Phosphaturic Mesenchymal Tumor

2020 ◽  
Vol 13 (3) ◽  
pp. 1373-1380
Author(s):  
Simon Häfliger ◽  
Ann-Katrin Seidel ◽  
Eric Schoch ◽  
Jan Reichmann ◽  
Damian Wild ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Fibroblast Growth Factor 23 ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Mesenchymal Tumor ◽  
Surgical Removal ◽  
Phosphaturic Mesenchymal Tumor ◽  
Peptide Receptor ◽  
Wasting Syndrome ◽  
Fgf 23

Tumor-induced osteomalacia is a very rare paraneoplastic syndrome. It can be caused by phosphaturic mesenchymal tumor (PMT), a generally benign tumor that produces fibroblast growth factor 23 (FGF-23), which can cause a severe renal phosphate wasting syndrome. Upon complete surgical removal of the tumor, FGF-23 normalizes and the osteomalacia is cured. In cases in which surgery is not feasible, radiofrequency ablation (RFA) is the treatment of choice. We describe a case with a PMT situated in the sacrum, in close proximity to the sacral plexus. Both surgery and RFA were considered potentially nerve damaging. Since the tumor showed expression of somatostatin receptors, we opted for a peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTATOC. However, the therapy did not show the expected success, since the FGF-23 level had even temporarily increased. The patient was then successfully treated with RFA. A partial remission of the tumor was achieved and FGF-23 levels nearly normalized. Despite some severe neurological side effects, the patient showed a remarkable clinical improvement, with no symptoms of osteomalacia within a few weeks.

scholarly journals Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review

2021 ◽  
Vol 10 (6) ◽  
pp. 1267
Author(s):  
Baptiste Camus ◽  
Anne-Ségolène Cottereau ◽  
Lola-Jade Palmieri ◽  
Solène Dermine ◽  
Florence Tenenbaum ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Phase Iii ◽  
Treatment Modalities ◽  
High Dose ◽  
Double Dose ◽  
Peptide Receptor ◽  
Phase Iii Study

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are 90Y-DOTATOC and 177Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared177Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy.

scholarly journals Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 34
Author(s):  
Cornelia Then ◽  
Evelyn Asbach ◽  
Harald Bartsch ◽  
Niklas Thon ◽  
Christian Betz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Olfactory Neuroblastoma ◽  
Mesenchymal Tumor ◽  
Fibroblast Growth ◽  
Phosphaturic Mesenchymal Tumor ◽  
Oncogenic Osteomalacia ◽  
Pet Ct ◽  
Fgf 23

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

scholarly journals Calculation of absorbed dose due to the 90Y-DOTATOC peptide receptor radionuclide therapy by MCNP5/X

2018 ◽  
Vol 33 (4) ◽  
pp. 380-385
Author(s):  
Marija Jeremic ◽  
Milovan Matovic ◽  
Suzana Pantovic ◽  
Dragoslav Nikezic ◽  
Dragana Krstic
Keyword(s):  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Computer Software ◽  
Absorbed Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Beta Radiation ◽  
Bremsstrahlung Radiation ◽  
Peptide Receptor ◽  
Beta Emitters ◽  
Good Expression

Strong beta emitters, like 90Y, 177Lu labelled peptide, are used for treatment of neuroendocrine tumours where there is a good expression of somatostatin receptors. In this work, MCNP5/X computer software and ORNL human phantoms were used to calculate absorbed dose due to 90Y labelled DOTATOC in the peptide receptor radionuclide therapy. Tumour was considered as a sources of beta radiation and represented as a sphere with diameter of 1-4 cm and 5 cm in liver, pancreas, and lungs. Results are expressed as absorbed dose per unit of cumulated activity, S ? value in units mGy?(MBq?s)?1. The far largest dose is in tumour itself, then in organ which contains the tumour. Doses in other organs, where the metastasis are the most frequent, due to the bremsstrahlung radiation, are much smaller and could be neglected. The largest dose, 8.66?10?3 mGy?(MBq?s)?1 was obtained for tumour with size of 3 cm.

scholarly journals SAT-502 Clinical Hypothyroidism Associated with Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma: A Novel Adverse Effect of Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sriram Gubbi ◽  
Mohammad Al-Jundi ◽  
Abhishek Jha ◽  
Marianne Knue ◽  
Joy Zou ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Radionuclide Therapy ◽  
Somatostatin Receptors ◽  
Standardized Uptake Value ◽  
Cervical Lymphadenopathy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Thyroid Peroxidase ◽  
Thyroid Function Tests ◽  
Subclinical Hyperthyroidism ◽  
Peptide Receptor

Abstract Background: Peptide receptor radionuclide therapy (PRRT) is a relatively novel, emerging therapy for the treatment of metastatic pheochromocytoma and paraganglioma (PPGL). Lutetium 177 (177Lu)-DOTATATE (Lutathera ®) is a form of PRRT that is currently being evaluated for its treatment efficacy in metastatic PPGL. It acts by binding to somatostatin receptors 2 (SSTR2) which are present on PPGL and other tissues of neuroendocrine origin. Although subclinical thyroid dysfunction has been previously noted, development of clinical hypothyroidism post 177Lu-DOTATATE therapy has not been reported to date. Case: A 29-year-old male with Beckwith-Weidemann syndrome and metastatic, succinate dehydrogenase subunit B (SDHB) germline mutation-positive paraganglioma with normal metanephrines was enrolled at our center under the 177Lu-DOTATATE trial for the treatment of inoperable, metastatic PPGL (ClinicalTrials.gov NCT03206060). Prior to the first cycle of therapy, the patient underwent endocrine evaluation per protocol. He was noted to have suppressed thyroid stimulating hormone (TSH) of &lt;0.01 mcIU/mL (normal: 0.27 - 4.2 mcIU/mL), and a normal free thyroxine (FT4) of 1.3 ng/dL (0.9 - 1.7 ng/dL), indicating subclinical hyperthyroidism. Thyroid auto-antibodies were not measured at that time point. The patient denied symptoms of hyper- or hypothyroidism. On physical examination, there was no thyromegaly or cervical lymphadenopathy. Serial monitoring of thyroid function tests (TFTs) was pursued. One month after the first cycle of 177Lu-DOTATATE therapy, the patient complained of new onset fatigue and weight gain. The TSH had markedly increased (73.04 mcIU/mL), along with a reduction in FT4 levels (0.3 mg/dL). Mass spectrometry measures revealed a low total T4 (1.3 ng/dL; 4.9 - 10.5 ng/dL), and a low total T3 (57 ng/dL; 87 - 169 ng/dL). Thyroid peroxidase antibodies were &gt;1000 IU/mL (0.0 - 34.9 IU/mL), and anti-thyroglobulin antibodies were 668 IU/mL (0.0-40.0 IU/mL). Weight-based levothyroxine therapy was initiated and the follow-up TFTs normalized. The baseline diagnostic Gallium 68-DOTATATE scan performed prior to PRRT demonstrated an increased diffuse uptake in the entire thyroid gland (maximum standardized uptake value: 14.3) and post-treatment SPECT-CT scan revealed similar increased, diffuse 177Lu-DOTATATE uptake in the thyroid gland. The patient currently has stable metastatic disease and continues to be under 177Lu-DOTATATE therapy. Conclusion: We report the first known case of clinical hypothyroidism post 177Lu-DOTATATE therapy in a patient who likely had subclinical hyperthyroidism prior to treatment. The possible mechanism was development of thyroiditis. Further studies are necessary to evaluate the mechanisms of PRRT-induced endocrine abnormalities and their clinical implications.

scholarly journals Somatostatin receptor endoradiotherapy of neuroendocrine tumors: experience in Hungarian patients

2011 ◽  
Vol 152 (10) ◽  
pp. 392-397 ◽  
Author(s):  
Péter Reismann ◽  
Zoltán Kender ◽  
Gabriella Dabasi ◽  
Lídia Sréter ◽  
Károly Rácz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Theoretical Background ◽  
Neuroendocrine Cells ◽  
Peptide Receptor ◽  
The University

Beside conventional therapies for the treatment of neuroendocrine tumors, a new therapeutical approach, peptide receptor radionuclide therapy has been developed recently. There are two important features which make this therapy feasible: somatostatin receptors are strongly over-expressed in most neuroendocrine tumors resulting in a high tumor-to-background ratio and internalization of the somatostatin-receptor complex in neuroendocrine cells. Due to these features, neuroendocrine tumors can be treated with radiolabelled somatostatin analogues. For peptide receptor radionuclide therapy, somatostatin analogues are conjugated to a chelator that can bind a radionuclide. The most frequently used radionuclides for neuroendocrine tumor treatment are the β-emitter Yttrium-90 (90Y) and the β+γ emitter Lutetium-177 (177Lu). Candidates for somatostatin receptor endoradiotherapy are patients with progressive, metastatic, somatostatin-receptor positive neuroendocrine tumors. Many patients have been successively treated with this approach: according to international results major remission can be achieved in 25% of the cases. Although this therapy is still unavailable in Hungary, Hungarian patients can be treated with somatostatin receptor endoradiotherapy with financial support from the National Health Fund in a co-operation with the University of Basel since 2005. During the past 5 years, 51 Hungarian patients have been treated with this therapy. This review briefly summarizes the theoretical background, indications, effectiveness and side effects of somatostatin receptor endoradiotherapy and the authors present the first data obtained from Hungarian patients. Orv. Hetil., 2011, 152, 392–397.

scholarly journals Tratamento de Tumores Neuroendócrinos Gastroenteropancreáticos com 177Lu-DOTA-TATE: Experiência do Instituto Português de Oncologia do Porto

2016 ◽  
Vol 29 (11) ◽  
pp. 726 ◽  
Author(s):  
Inês Lucena Sampaio ◽  
Henrique Vara Luiz ◽  
Liliana Sobral Violante ◽  
Ana Paula Santos ◽  
Luís Antunes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Side Effects ◽  
Radionuclide Therapy ◽  
Liver Toxicity ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Symptomatic Improvement ◽  
Hematologic Toxicity ◽  
Safety And Efficacy ◽  
Peptide Receptor

Introduction: The purpose of this article is to report the experience of Instituto Português de Oncologia do Porto in the treatment of gastroenteropancreatic neuroendocrin tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality.Material and Methods: A retrospective analysis of clinical reports of patients with gastrentheropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed.Results: Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p < 0.05).Discussion: Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is an effective, secure and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases.Conclusion: Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastrentheropancreatic neuroendocrin tumors, with demonstrated benefits in terms of safety and efficacy.

scholarly journals Lutathera®: The First FDA- and EMA-Approved Radiopharmaceutical for Peptide Receptor Radionuclide Therapy

2019 ◽  
Vol 12 (3) ◽  
pp. 114 ◽  
Author(s):  
Ute Hennrich ◽  
Klaus Kopka
Keyword(s):  
Cell Death ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Double Strand Breaks ◽  
Somatostatin Analogue ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Strand Breaks ◽  
Peptide Receptor

As the first radiopharmaceutical for Peptide Receptor Radionuclide Therapy (PRRT), Lutathera® was approved by the EMA in 2017 and the FDA in 2018 for the treatment of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors. Using the concept of PRRT, Lutathera® combines the radionuclide 177Lu with the somatostatin analogue DOTA-TATE, thus delivering ionizing radiation specifically to tumor cells expressing somatostatin receptors. As a result, DNA single- and double-strand breaks are provoked, in case of double-strand breaks leading to cell death of the tumor and its SSTR-positive lesions.

Peptide Receptor Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors

2019 ◽  
Vol 03 (01) ◽  
pp. 071-080
Author(s):  
Ghassan El-Haddad
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Large Scale ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Peptide Receptor

AbstractPeptide receptor radionuclide therapy (PRRT), a targeted form of systemic radiotherapy allowing the delivery of radionuclides directly to tumor cells, has been used for more than three decades in the treatment of advanced neuroendocrine tumors (NETs) exhibiting high levels of somatostatin receptors. Recently, 177Lu-DOTATATE, a radiolabeled somatostatin analog, was approved by the US Food and Drug administration for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults. Early phase I and II studies have shown the benefits of PRRT, but it was the NETTER-1 trial (a large-scale randomized multicenter trial for progressive well-differentiated advanced or metastatic somatostatin receptor-positive midgut carcinoid tumors) that provided high-level evidence of improved overall response rate, and progression-free survival compared with long-acting octreotide. In this article, we will discuss the evolution, clinical applications, and implementation of PRRT, as well as potential future strategies to enhance its clinical efficacy in the treatment of GEP-NETs.

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