Preparation and preclinical evaluation of 177Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors

Beckford-Vera, Denis; Eigner, Sebastian; Henke, Kateřina Eigner; Lebeda, O.; Melichar, F.; Beran, M.

doi:10.1016/j.nucmedbio.2011.07.001

Cited by 33 publications

(6 citation statements)

References 36 publications

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“…Uptake of 177 Lu-9E7.4 mAb was also high in the spleen (27.6 ± 8.2% ID/g tissue between 2 and 48 h) and in the intestines (18.8 ± 9.1% ID/g tissue at 24 and 48 h) (Figure 4 ). Finally, accumulation of the 177 Lu-9E7.4 mAb in other healthy organs was similar to what has been described with other radioimmunoconjugates ( 38 ).…”

Section: Resultssupporting

confidence: 87%

Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model

et al. 2015

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ObjectivesRadioimmunotherapy (RIT) has emerged as a potential treatment option for multiple myeloma (MM). In humans, a dosimetry study recently showed the relevance of RIT using an antibody targeting the CD138 antigen. The therapeutic efficacy of RIT using an anti-CD138 antibody coupled to 213Bi, an α-emitter, was also demonstrated in a preclinical MM model. Since then, RIT with β-emitters has shown efficacy in treating hematologic cancer. In this paper, we investigate the therapeutic efficacy of RIT in the 5T33 murine MM model using a new anti-CD138 monoclonal antibody labeled either with 213Bi for α-RIT or 177Lu for β-RIT.MethodsA new monoclonal anti-CD138 antibody, 9E7.4, was generated by immunizing a rat with a murine CD138-derived peptide. Antibody specificity was validated by flow cytometry, biodistribution, and α-RIT studies. Then, a β-RIT dose-escalation assay with the 177Lu-radiolabeled 9E7.4 mAb was performed in KalwRij C57/BL6 mice 10 days after i.v. engraftment with 5T33 MM cells. Animal survival and toxicological parameters were assessed to define the optimal activity.Resultsα-RIT performed with 3.7 MBq of 213Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared to 37 days for the untreated control and effected cure in 45% of animals. β-RIT performed with 18.5 MBq of 177Lu-labeled 9E7.4 mAb was well tolerated and significantly increased mouse survival (54 vs. 37 days in the control group); however, no mice were cured with this treatment.ConclusionThis study revealed the advantages of α-RIT in the treatment of MM in a preclinical model where β-RIT shows almost no efficacy.

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Section: Resultssupporting

confidence: 87%

Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model

et al. 2015

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“…hR3 has demonstrated very encouraging results in paediatric pontine (brainstem) and adult gliomas. hR3 has shown promising results in clinical trials in non‐small cell lung cancer and in a monotherapy trial in patients with advanced metastatic pancreatic cancer . In vitro studies were performed on the immortalized human cancer cell line A431 (human squamous carcinoma) and on the HaCaT cell line (human keratinocyte), both of which express high levels of the ErbB1 receptor…”

Section: Introductionmentioning

confidence: 99%

Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

Bárta

Lázníčková

Lázníček

et al. 2013

Labelled Comp Radiopharmac

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The choice of radiolabel and the manner of its attachment to nimotuzumab had little effect on the internalization of the antibody into ErbB1-expressing cell lines. However, the type of radiolabel, the way in which it was attached to nimotuzumab and the radiolabelling procedure, significantly affected the blood clearance, liver uptake and liver persistence of radiolabelled nimotuzumab. (131) I-nimotuzumab had the longest elimination half-life and the lowest radioactivity uptake in the liver. (177) Lu-labelled nimotuzumab exhibited a shorter elimination half-life, high radioactivity and long-term retention in the liver.

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“…Another EGFR mAb used to treat pediatric brain tumors is nimotuzumab, which could be safely administered over long periods, and was associated with improved survival in 23 high-grade glioma patients [187] . The potential use of nimotuzumab in radioimmunotherapy (when conjugated to (177)Lu) was also recently tested in A431 epithelial carcinoma xenografts, where locoregional application demonstrated antitumor activity [188] . Less encouragingly, discordant responses in adult versus pediatric high-grade glioma patients have been reported for bevacizumab.…”

Section: Relevant Biomarkers In Childhood Malignancies and Novel Thermentioning

confidence: 99%

Molecular profiling of childhood cancer: Biomarkers and novel therapies

et al. 2014

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BackgroundTechnological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies.Scope of reviewThis review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type.Major conclusionsThere is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies.General significanceThe increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

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Preparation and preclinical evaluation of 177Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors

Cited by 33 publications

References 36 publications

Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model

Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model

Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

Molecular profiling of childhood cancer: Biomarkers and novel therapies

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