Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Izquierdo-Sánchez, Vanessa; Muñiz-Hernández, Saé; Vázquez-Becerra, Héctor; Pacheco‐Yépez, Judith; Romero-Piña, Mario E.; Arrieta, Óscar; Medina, Luis Alberto

doi:10.3390/molecules23123138

Cited by 3 publications

(5 citation statements)

References 44 publications

(66 reference statements)

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“…The splenic and bone uptakes seen with 89 Zr-ch806 were a result of catabolized free 89 Zr and similar to that seen with other 89 Zr-labeled antibodies [ 30 , 31 , 32 ]. Similarly, levels of tracer uptake in the liver were consistent with other studies evaluating other radioconjugates conjugated to anti-EGFR antibodies [ 24 , 29 ].…”

Section: Discussionsupporting

confidence: 89%

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Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma

et al. 2020

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Epidermal growth factor receptor (EGFR) is highly overexpressed in malignant mesothelioma (MM). MAb806 is a novel anti-EGFR antibody that selectively targets a tumor-selective epitope. MAb806-derived antibody drug conjugates (ADCs), ABT-414, ABBV-221 and ABBV-322, may represent a novel therapeutic strategy in MM. EGFR and mAb806 epitope expressions in mesothelioma cell lines were evaluated using an array of binding assays, and the in vitro cell effects of ABT-414 and ABBV-322 were determined. In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor models. We also performed biodistribution and imaging studies to allow the quantitative targeting of MM by mAb806 using a 89Zr-labeled immunoconjugate—ch806. A high EGFR expression was present in all mesothelioma cell lines evaluated and mAb806 binding present in all cell lines, except NCIH-2452. ABT-414 and ABBV-322 resulted in significant tumor growth inhibition in MM models with high EGFR and mAb806 epitope expressions. In contrast, in an EGFR-expressing PDX model that was negative for the mAb806 epitope, no growth inhibition was observed. We demonstrated the specific targeting of the mAb806 epitope expressing MM tumors using 89Zr-based PET imaging. Our data suggest that targeting EGFR in MM using specific ADCs is a valid therapeutic strategy and supports further investigation of the mAb806 epitope expression as a predictive biomarker.

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Section: Discussionsupporting

confidence: 89%

“…Previous preclinical studies have evaluated the use of radiolabeled anti-EGFR antibodies using a variety of radioconjugates, with mixed results ([ 4 , 28 , 29 ]. This study demonstrated the specific targeting of mAb806-expressing MM tumors using 89 Zr-based PET imaging.…”

Section: Discussionmentioning

confidence: 99%

Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma

et al. 2020

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“…Antibody-based therapy has deep roots in the history of biotechnologies. In fact, starting from serotherapy institutes (such as The Institute of Serotherapy and Vaccination of Tuscany), where active immunization against specific antigens was induced in large animals, such as horses, in order to use their plasma as a medical tool, subsequently we finally reached a more sophisticated biotechnological product [4,61].…”

Section: Small Molecules Peptides and Antibody In Targeted Therapymentioning

confidence: 99%

“…Promising results also come from the use of a humanized anti-EGFR (epidermal growth factor receptor) antibody, Nimotuximab (h-R3) [61]. In the study in question, the researchers wanted to evaluate antibody biodistribution, uptake on the tumor site and binding affinity for EGFR.…”

Section: Future Perspective: the Challenge In The Exploitation Of Evsmentioning

confidence: 99%

“…In the study in question, the researchers wanted to evaluate antibody biodistribution, uptake on the tumor site and binding affinity for EGFR. The study was conducted in vivo on MPM xenograft models, radiolabeling the antibody with Gallium-67, demonstrating a remarkable uptake of the antibody-radiolabeled complex at the tumor site [61].…”

Section: Future Perspective: the Challenge In The Exploitation Of Evsmentioning

confidence: 99%

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Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

Burgio

Noori

Gammazza

et al. 2020

IJMS

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Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

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Nuclear Medicine Techniques for in Vivo Animal Imaging

Финогенова¹,

Липенгольц

Smirnova³

et al. 2020

Sib. onkol. ž.

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The object of the study was to analyze radionuclide detection techniques for in vivo animal imaging. Material and Methods. A total of 49 publications available from Scopus, Web of Science, Google Scholar eLIBRARY and Pubmed and published between 2013 and 2019 were reviewed. Results. The nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are the most suitable imaging modalities for in vivo animal imaging. Besides traditional radiopharmaceuticals, such as [18F]-FDG and [99mTc]-MDP, the new radiolabeled tracers, such as [99mTc]-3PRGD2, [ 99mTc]-HisoDGR targeted to integrin, [18F]- tetrafluoroborate, labeled antibodies and others have been used for the noninvasive detection of tumors and for monitoring their response to treatment in mice and rats. 111In and 89Zr –labeled monoclonal antibodies are used to evaluate the expression level of many receptors such as EGFR, HER-2 and others in different tumors. PET imaging has demonstrated a good efficacy in tumor hypoxia imaging with [64Cu]-ATSM, [18F]-FMISO. PET and SPECT can also be used for early evaluation of anticancer therapy response. Nuclear imaging techniques may assist in the vivo assessment of DNA damage (doubleand single-strand brakes) as well as apoptosis intensity in tumor and normal tissues. [99mTc]- duramycin is the most commonly used tracer for imaging of apoptosis. Changes in tumor cell proliferation in response to anticancer therapy can be assessed by PET imaging with [18F]-FLT. Conclusion. Nuclear medicine offers a unique means to study cancer biology in vivo and to optimize cancer therapy.

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Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Cited by 3 publications

References 44 publications

Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma

Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

Nuclear Medicine Techniques for in Vivo Animal Imaging

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