Les anticorps radiomarqués pour le traitement des cancers

Barbet, Jacques; Chatal, Jean‐François; Kraeber-Bodéré, Françoise

doi:10.1051/medsci/200925121039

Cited by 6 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Les questions qui se posent aujourd'hui ne concernent donc plus l'efficacité des RIC, mais surtout leur expansion et leur positionnement dans le traitement des tumeurs solides [6]. La première évaluation d'un anticorps conjugué à une molécule cytotoxique dans un modèle tumoral murin a été publiée par G. Mathé et al en 1958 [7].…”

Section: Un Développement Clinique Riche En Rebondissements…unclassified

La montée en puissance des immunoconjugués en oncologie

Vigne

Sassoon

2014

Med Sci (Paris)

View full text Add to dashboard Cite

Section: Un Développement Clinique Riche En Rebondissements…unclassified

La montée en puissance des immunoconjugués en oncologie

Vigne

Sassoon

2014

Med Sci (Paris)

View full text Add to dashboard Cite

“…There are several therapeutic radionuclides that are used in combination with antibodies or being subject of recent investigations aiming for radioimmunotherapeutic applications including the β − -emitters 67 Cu, 90 Y, 131 I and 177 Sharkey and Goldenberg 2011; Yeong et al 2014). Since it could be shown that smaller tumors and metastases are more accessible for radiolabeled antibodies than large ones and thus show a better response to this treatment, RIT is a promising tool especially for therapy of cancer even before tumors or lesions become detectable via imaging methods or in advanced stages of metastatic diseases (Barbet et al 2012; Barbet et al 2009). In this case, β − -emitting radionuclides with comparatively low β − -energy are the best choice to minimize the damage to surrounding healthy tissue while destroying malignant cells in the target.…”

Section: Introductionmentioning

confidence: 99%

AAZTA5-squaramide ester: promising tool for 177Lu-labeling of monoclonal antibodies under mild conditions

Klasen¹,

Moon²,

Rösch³

2020

Preprint

View full text Add to dashboard Cite

Background Combining the advantages of both cyclic and acyclic chelator systems, AAZTA (1,4-bis(carboxymethyl)‐6‐[bis(carboxymethyl)]amino‐6‐methylperhydro‐1,4‐diazepine) is well suited for complexation of various diagnostic and therapeutic radiometals such as gallium-68, scandium-44 and lutetium-177 under mild conditions. Due to its specificity for primary amines and pH dependent binding properties, squaric acid (SA) represents an excellent tool for selective coupling of the appropriate chelator to different target vectors. Therefore, the aim of this study was to evaluate radiolabeling properties of the novel bifunctional AAZTA5-SA being coupled to a model antibody (bevacizumab) in comparison to DOTA-SA using the therapeutic nuclide lutetium-177. Results As proof-of-concept, bevacizumab was first functionalized with either AAZTA5-SA or DOTA-SA. After purification via fractionated size exclusion chromatography (SEC), the corresponding immunoconjugates were subsequently radiolabeled with lutetium-177 at pH 7 and room temperature (RT) as well as 37 °C. After 90 min, labeling of AAZTA5-SA-mAb resulted in almost quantitative radiochemical yields (RCY) of > 98% and > 99%, respectively. After purification via SEC, the radioconjugate [177Lu]Lu-AAZTA5-SA-mAb could be obtained with a purity of > 99% and an apparent specific activity of 4.5 GBq/µmol. In contrast, 177Lu-labeling of DOTA-SA-mAb showed negligible radiochemical yields of < 2% both at room temperature and 37 °C. In vitro complex stability measurements of [177Lu]Lu-AAZTA5-SA-mAb in human serum at 37 °C indicated > 99% protein bound activity within 15 days. In phosphate buffered saline (PBS), a slightly decreased stability of > 93% intact conjugate was observed over the same period. Conclusion Coupling of AAZTA5-SA to the monoclonal antibody bevacizumab allowed for 177Lu-labeling with almost quantitative radiochemical yields both at room temperature and 37 °C. Within 15 days, the resulting radioconjugate indicated very high in vitro complex stability both in human serum and PBS. Therefore, AAZTA5-SA is a promising tool for 177Lu-labeling of sensitive biomolecules such as antibodies for theranostic applications.

show abstract

Radiolabeled Antibodies for Cancer Imaging and Therapy

Barbet

Bardiès

Bourgeois

et al. 2012

Methods in Molecular Biology

View full text Add to dashboard Cite

Radiolabeled antibodies were studied first for tumor detection by single-photon imaging, but FDG PET stopped these developments. In the meantime, radiolabeled antibodies were shown to be effective in the treatment of lymphoma. Radiolabeling techniques are well established and radiolabeled antibodies are a clinical and commercial reality that deserves further studies to advance their application in earlier phase of the diseases and to test combination and adjuvant therapies including radiolabeled antibodies in hematological diseases. In solid tumors, more resistant to radiations and less accessible to large molecules such as antibodies, clinical efficacy remains limited. However, radiolabeled antibodies used in minimal or small-size metastatic disease have shown promising clinical efficacy. In the adjuvant setting, ongoing clinical trials show impressive increase in survival in otherwise unmanageable tumors. New technologies are being developed over the years: recombinant antibodies and pretargeting approaches have shown potential in increasing the therapeutic index of radiolabeled antibodies. In several cases, clinical trials have confirmed preclinical studies. Finally, new radionuclides, such as lutetium-177, with better physical properties will further improve the safety of radioimmunotherapy. Alpha particle and Auger electron emitters offer the theoretical possibility to kill isolated tumor cells and microscopic clusters of tumor cells, opening the perspective of killing the last tumor cell, which is the ultimate challenge in cancer therapy. Preliminary preclinical and preliminary clinical results confirm the feasibility of this approach.

show abstract

Les anticorps radiomarqués pour le traitement des cancers

Cited by 6 publications

References 35 publications

La montée en puissance des immunoconjugués en oncologie

La montée en puissance des immunoconjugués en oncologie

AAZTA5-squaramide ester: promising tool for 177Lu-labeling of monoclonal antibodies under mild conditions

Radiolabeled Antibodies for Cancer Imaging and Therapy

Contact Info

Product

Resources

About