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

Hennrich, Ute; Kopka, Klaus

doi:10.3390/ph12030114

Cited by 260 publications

(219 citation statements)

References 21 publications

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“…The obtained data shows a steep drop in survival, which was expected due to the high-LET nature of Auger electrons. Comparison with EBIR allowed us to calculate the RBE, which corroborated the potential of Auger-emitting molecules for targeted radiotherapy, a fast-growing and promising field (41,42). This proved to be a significant improvement compared to a previously-published version of the molecule, 131 I-PARPi, where the RBE of the emitted electron is significantly lower.…”

Section: Discussionsupporting

confidence: 58%

Targeted Brain Tumor Radiotherapy Using an Auger Emitter

Pirovano

Jannetti

Carter

et al. 2020

Clinical Cancer Research

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Glioblastoma multiforme is a highly aggressive form of brain cancer whose location, tendency to infiltrate healthy surrounding tissue, and heterogeneity significantly limit survival, with scant progress having been made in recent decades. Experimental design 123 I-MAPi (Iodine-123 Meitner-Auger PARP1 inhibitor) is a precise therapeutic tool composed of a PARP1 inhibitor radiolabeled with an Auger-and gamma-emitting iodine isotope. Here, the PARP inhibitor, which binds to the DNA repair enzyme PARP1, specifically targets cancer cells, sparing healthy tissue, and carries a radioactive payload within reach of the cancer cells' DNA. Results The high relative biological efficacy of Auger electrons within their short range of action is leveraged to inflict DNA damage and cell death with high precision. The gamma ray emission of 123 I-MAPi allows for the imaging of tumor progression and therapy response, and for patient dosimetry calculation. Here we demonstrated the efficacy and specificity of this small molecule radiotheranostic in a complex preclinical model. In vitro and in vivo studies demonstrate high tumor uptake and a prolonged survival in mice treated with 123 I-MAPi when compared to vehicle controls. Different methods of drug delivery were investigated to develop this technology for clinical applications, including convection enhanced delivery (CED) and intrathecal injection. Conclusions Taken together, these results represent the first full characterization of an Augeremitting PARP inhibitor which demonstrate a survival benefit in mouse models of GBM and confirm the high potential of 123 I-MAPi for clinical translation.

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Section: Discussionsupporting

confidence: 58%

Targeted Brain Tumor Radiotherapy Using an Auger Emitter

Pirovano

Jannetti

Carter

et al. 2020

Clinical Cancer Research

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“…As for targeted therapy, everolimus demonstrated its high e cacy and tolerability, especially when in combination with other drugs in some clinical studies [22,23]. PRRT has also been recognized as an alternative therapy for unresectable or metastatic NEN, of which 177 Lu-DOTATATE was approved to treat GEP-NEN patients in with SSTR positive expression among both Europe and the United States [24,25]. Apart from them, supportive therapy cannot be ignored debulking surgery and interventional radiologic techniques to reduce tumors bulk or load, as well as systemic medical treatment options to manage or prevent hypersecretion syndromes and treatment-related side effects.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features and Prognosis of Gastric Neuroendocrine Neoplasms

Wang

Wen

Tian

et al. 2020

Preprint

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Abstract Purpose: We performed a retrospective study to investigate the relationship between clinicopathological features and prognosis of G-NEN.Methods: Clinicopathological features and follow-up data of 67 patients with G-NEN treated at Shandong Provincial Hospital affiliated of Shandong University were analyzed retrospectively. Results: This whole cohort included 53 males and 14 females, with a mean age of 59.37±9.80 years. The clinical symptoms and the primary tumor site were not specific. Neuroendocrine tumor, neuroendocrine carcinoma, and mixed neuroendocrine–non‐neuroendocrine neoplasm accounted for 14.93%, 59.70%, and 25.37%, respectively. TNM stages Ⅰ-Ⅳ: 6, 6, 49, 4, respectively. All patients underwent surgically treated. Forty-five patients underwent laparoscopic surgery, and twenty-two patients received an open approach. The median survival time was 36 months in all patients. The overall survival rate for the entire cohort was 68.1 %, 44.7 %, and 34.5% at 1, 3, and 5 years, respectively. Logistic regression analysis revealed that the invasive depth of tumors was predictors for metastasis. The univariate analysis confirmed that smoking, T stage, distant metastasis, and surgical method were related to survival. COX regression analysis showed that the T stage (HR=4.817, 95%CI: 1.021-22.729, P=0.047) was an independent risk factor for evaluating the prognosis of patients with G-NEN.Conclusions: G-NEN is a kind of rare tumors that can occur at any part of the stomach. The clinical features are not specific. The tumor invasive depth related to tumor metastasis. The prognosis is associated with smoking, T stage, distant metastasis, and surgical method. Of them, T stage is an independent prognostic factor for G-NEN patients. But larger studies are needed in the future.

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“…Such a pair of theranostic tracers is represented, among others, by the diagnostic [ 68 Ga]Ga-DOTA-TOC and its therapeutic partner [ 177 Lu]Lu-DOTA-TATE (DOTA-(D-Phe 1 ,Tyr 3 )-octreotate, Lutathera ® (AAA, France)). [ 177 Lu]Lu-DOTA-TATE was approved by the EMA and the FDA in 2017 and 2018, respectively, as the first radiopharmaceutical for peptide receptor radionuclide therapy [9][10][11]. In the case of this theranostic pair, one cannot speak of a true pair of identical theranostic radiopharmaceuticals since the imaging tracer uses the SSTR binding peptide DOTA-TOC, while the therapeutic peptide uses DOTA-TATE instead.…”

Section: Introductionmentioning

confidence: 99%

[68Ga]Ga-DOTA-TOC: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging

2020

Self Cite

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In the United States, [68Ga]Ga-DOTA-TOC has been approved by the Food and Drug Administration (FDA) in 2019 as the first 68Ga-radiopharmaceutical for imaging of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors while employing positron emission tomography (PET). In Europe (Austria, Germany, France), [68Ga]Ga-DOTA-TOC was already approved back in 2016. This radiopharmaceutical combines the radionuclide 68Ga with the somatostatin analogue DOTA-TOC for specific imaging of tumor cells expressing SSTRs. Such a targeting approach can also be used for therapy planning in the case of both localized as well as disseminated disease and potentially for the evaluation of treatment response.

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

Cited by 260 publications

References 21 publications

Targeted Brain Tumor Radiotherapy Using an Auger Emitter

Targeted Brain Tumor Radiotherapy Using an Auger Emitter

Clinicopathological Features and Prognosis of Gastric Neuroendocrine Neoplasms

[68Ga]Ga-DOTA-TOC: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging

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