Radioinmunoterapia en el linfoma no Hodgkin, posicionamiento, seguridad y eficacia de 90Y-ibritumomab. Experiencia y seguimiento a los 10 años

Martínez, Ándrés García; Martínez-Ramírez, Mario Alberto; Martínez-Caballero, D.; Beneit, Paola; Clavel, Jacqueline; Figueroa, Germán G.; Verdú, J.

doi:10.1016/j.remn.2016.05.004

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Currently, one mAb-based TRNT agent is commercially used, i.e. the anti-CD20 mAb 90 Y-ibritumomab for treating B cell non-Hodgkin lymphoma (9–11). Peptide receptor radionuclide therapy (PRRNT) shows efficacy in patients with neuroendocrine tumors (12) and is currently also being investigated in prostate and pancreatic carcinomas (12,13).…”

Section: Introductionmentioning

confidence: 99%

131I-labeled Anti-HER2 Camelid sdAb as a Theranostic Tool in Cancer Treatment

D’Huyvetter

Vos

Xavier

et al. 2017

Clinical Cancer Research

149

152

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Purpose Camelid single-domain antibody-fragments (sdAbs) have beneficial pharmacokinetic properties, and those targeted to HER2 can be used for imaging of HER2-overexpressing cancer. Labeled with a therapeutic radionuclide, they may be used for HER2-targeted therapy. Here we describe the generation of a 131I-labeled sdAb as a theranostic drug to treat HER2-overexpressing cancer. Experimental design Anti-HER2 sdAb 2Rs15d was labeled with 131I using [131I]SGMIB and evaluated in vitro. Biodistribution was evaluated in two HER2+ murine xenograft models by micro-SPECT/CT imaging and at necropsy, and under challenge with trastuzumab and pertuzumab. The therapeutic potential of [131I]SGMIB-2Rs15d was investigated in two HER2+ tumor mouse models. A single-dose toxicity study was performed in mice using unlabeled [127I]SGMIB-sdAb at 1.4mg/kg. The structure of the 2Rs15d-HER2 complex was determined by X-ray crystallography. Results [131I]SGMIB-2Rs15d bound specifically to HER2+ cells (KD=4.74±0.39nM). High and specific tumor uptake was observed in both BT474/M1 and SKOV-3 tumor xenografted mice and surpassed kidney levels by 3h. Extremely low uptake values were observed in other normal tissues at all time points. The crystal structure revealed that 2Rs15d recognizes HER2 Domain 1, consistent with the lack of competition with trastuzumab and pertuzumab observed in vivo. [131I]SGMIB-2Rs15d alone, or in combination with trastuzumab extended median survival significantly. No toxicity was observed after injecting [127I]SGMIB-2Rs15d. Conclusions These findings demonstrate the theranostic potential of [131I]SGMIB-2Rs15d. An initial scan using low radioactive [*I]SGMIB-2Rs15d allows patient selection and dosimetry calculations for subsequent therapeutic [131I]SGMIB-2Rs15d, and could thereby impact therapy outcome on HER2+ BC patients.

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Section: Introductionmentioning

confidence: 99%

131I-labeled Anti-HER2 Camelid sdAb as a Theranostic Tool in Cancer Treatment

D’Huyvetter

Vos

Xavier

et al. 2017

Clinical Cancer Research

149

152

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“…O diagnóstico definitivo foi compatível com LNH difuso de alto grau, com imunofenótipo B, primário do baço. Não havia sinais de comprometimento neoplásico nos tecidos adjacentes ao órgão retirado, estando a neoplasia restrita ao baço 8 , contrariando o caráter altamente infiltrativo do LNH de imunofenótipo B 9 . Assim, além de corroborar a definição do diagnóstico preciso, o procedimento cirúrgico permitiu a retirada completa do tumor.…”

Section: Relato Do Casounclassified

Diagnóstico Histopatológico e Imuno-histoquímico de Linfoma de Baço com Apresentação Clínica Atípica: Relato de Caso

Fragoso¹,

Santos²,

Marques³

et al. 2021

Rev. Bras. Cancerol.

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Introdução: Tanto o angiossarcoma esplênico quanto o linfoma não Hodgkin (LNH) de células B não só são raros como apresentam desafios diagnósticos. Relato do caso: Paciente do sexo masculino, 45 anos, obeso, sudorese noturna há um ano, e dor abdominal cíclica há dois, com clínica inicial de angiossarcoma, contudo, sob o exame histopatológico e imuno-histoquímico, mostrou tratar-se de LNH de células B com apresentação atípica. A ultrassonografia (US) de abdome total realizada ao início do sintoma de sudorese noturna não teve alterações. Após um ano, a US apresentou massa esplênica. Na ressonância magnética da região abdominal, constatou-se tumoração esplênica expansiva heterogênea no aspecto anterior, suspeita de angiossarcoma esplênico. Após esplenectomia total, pancreatectomia caudal e linfadenectomia retroperitoneal, o exame histopatológico mostrou neoplasia maligna pouco diferenciada extensamente necrótica substituindo o parênquima esplênico. O estudo imuno-histoquímico foi positivo para os marcadores CD20 em diversos focos, para o BCL2 e para o KI67 (em 95% dos núcleos das células neoplásicas). A histopatologia e a imuno-histoquímica foram compatíveis com o diagnóstico de LNH difuso de alto grau, com imunofenótipo B do baço, sem sinal de infiltração de tecidos adjacentes. Após a esplenectomia total e quatro ciclos de quimioterapia, o paciente estava livre do linfoma e sem sintomas. Conclusão: É de suma importância o reconhecimento do diagnóstico correto de neoplasias raras como a relatada. Tanto a clínica quanto os exames de imagem, mesmo que fundamentais, podem ser imprecisos, reiterando a importância dos exames histológico e imuno-histoquímico complementares.

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“…Yet, RIT has also had the opportunity to shine in oncohaematology. In 2004, 90Yttrium-labelled ibritumomab tiuxetan, a mAb targeting CD20, was approved following several clinical studies demonstrating its efficacy in non-Hodgkin B-cell lymphoma (NHL) [101][102][103][104]. In September 2009, it was even approved by the FDA as a first-line therapy for follicular lymphoma patients [105].…”

Section: What's More?mentioning

confidence: 99%

ImmunoPET in Multiple Myeloma—What? So What? Now What?

Bailly

Chalopin

Gouard

et al. 2020

Cancers

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Despite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity and resolution of a PET camera with the specificity of a radiolabelled mAb, holds the capability to cement this new treatment paradigm for MM patients. It has the potential to non-invasively monitor the distribution of therapeutic antibodies or directly monitor biomarkers on MM cells, and to allow direct observation of potential changes over time and in response to various therapeutic interventions. Tumor response could, in the future, be anticipated more effectively to provide individualized treatment plans tailored to patients according to their unique imaging signatures. This work explores the important role played by immunotherapeutics in the management of MM, and focuses on some of the challenges for this drug class and the significant interest of companion imaging agents such as immunoPET.

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Radioinmunoterapia en el linfoma no Hodgkin, posicionamiento, seguridad y eficacia de 90Y-ibritumomab. Experiencia y seguimiento a los 10 años

Cited by 7 publications

References 27 publications

131I-labeled Anti-HER2 Camelid sdAb as a Theranostic Tool in Cancer Treatment

131I-labeled Anti-HER2 Camelid sdAb as a Theranostic Tool in Cancer Treatment

Diagnóstico Histopatológico e Imuno-histoquímico de Linfoma de Baço com Apresentação Clínica Atípica: Relato de Caso

ImmunoPET in Multiple Myeloma—What? So What? Now What?

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