Anti-HER2 monoclonal antibody based-radioimmunoconjugates: Assessment of the chelating agent influence

Miranda, Ana Cláudia Camargo; Durante, Ana Claudia R.; Fuscaldi, Leonardo Lima; Barbezan, Angélica Bueno; Lima, Cilene Rebouças de; Perini, Efrain Araujo; Araújo, Elaine Bortoleti de

doi:10.1016/j.bmc.2021.115996

Cited by 3 publications

(9 citation statements)

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“…The immuno- and radioimmunoconjugation were performed with no further modification from the previous proposed protocol [ 25 ], at a 1:20 (antibody:chelator) molar ratio. The RICs presented radiochemical purity >90%; however, for [ 177 Lu]Lu-DOTA-trastuzumab, the radiochemical yield was about 84% and, then it was necessary to perform the purification in a molecular exclusion column to achieve radiochemical purity >90%.…”

Section: Resultsmentioning

confidence: 99%

“…The number of chelators per antibody molecule may influence the radiochemical stability of the radioimmunoconjugate. Previous MALDI–TOF studies revealed an average number of 6–7 molecules of p-SCN-Bn-DTPA and 8–9 molecules of DOTA-NHS-ester coupled to trastuzumab for a 1:20 M ratio [ 25 ]. The [ 177 Lu]Lu-DOTA immunoconjugate showed greater stability in serum than [ 111 In]In-DTPA, especially in the first 4 h of incubation.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Immunoconjugation and radioimmunoconjugation were performed as previously described [25]. Briefly, the trastuzumab (Herceptin ® , Roche, Basileia, Switzerland), at an initial concentration of 10.5 mg•mL −1 , was previously purified by centrifugation using the concentrator tube (Amicon ® Ultra 10,000 MWCO, Merck Millipore, Burlington, MA, USA) with 0.2 M sodium bicarbonate buffer (pH 8.5) at 3000× g/4 • C. Conjugation to the bifunctional chelating agents p-SCN-Bn-DTPA and DOTA-NHS-ester (Macrocyclics, Plano, TX, USA) in a 1:20 (antibody:chelator) molar ratio, were performed by incubation at 37 • C and 350 rpm for 2 h. The volume of the immunoconjugation reaction was 1.5 mL.…”

Section: Immunoconjugation and Radioimmunoconjugationmentioning

confidence: 99%

“…The immuno-and radioimmunoconjugation were performed with no further modification from the previous proposed protocol [25], at a 1:20 (antibody:chelator) molar ratio.…”

Section: Immunoconjugation and Radioimmunoconjugationmentioning

confidence: 99%

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Radioimmunotheranostic Pair Based on the Anti-HER2 Monoclonal Antibody: Influence of Chelating Agents and Radionuclides on Biological Properties

et al. 2021

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The oncogene HER2 is an important molecular target in oncology because it is associated with aggressive disease and the worst prognosis. The development of non-invasive imaging techniques and target therapies using monoclonal antibodies is a rapidly developing field. Thus, this work proposes the study of the radioimmunotheranostic pair, [111In]In-DTPA-trastuzumab and [177Lu]Lu-DOTA-trastuzumab, evaluating the influence of the chelating agents and radionuclides on the biological properties of the radioimmunoconjugates (RICs). The trastuzumab was immunoconjugated with the chelators DTPA and DOTA and radiolabeled with [111In]InCl3 and [177Lu]LuCl3, respectively. The stability of the RICs was evaluated in serum, and the immunoreactive and internalization fractions were determined in SK-BR-3 breast cancer cells. The in vivo pharmacokinetics and dosimetry quantification and the ex vivo biodistribution were performed in normal and SK-BR-3 tumor-bearing mice. The data showed that there was no influence of the chelating agents and radionuclides on the immunoreactive and internalization fractions of RICs. In contrast, they influenced the stability of RICs in serum, as well as the pharmacokinetics, dosimetry and biodistribution profiles. Therefore, the results showed that the nature of the chelating agent and radionuclide could influence the biological properties of the radioimmunotheranostic pair.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Immunoconjugation and Radioimmunoconjugationmentioning

confidence: 99%

“…The immuno-and radioimmunoconjugation were performed with no further modification from the previous proposed protocol [25], at a 1:20 (antibody:chelator) molar ratio.…”

Section: Immunoconjugation and Radioimmunoconjugationmentioning

confidence: 99%

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Radioimmunotheranostic Pair Based on the Anti-HER2 Monoclonal Antibody: Influence of Chelating Agents and Radionuclides on Biological Properties

et al. 2021

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An ultra-sensitive fluorescent Aptamer sensor based on 2D MOF for detection of HER2 in serum

Li,

Zhang,

et al. 2023

Microchemical Journal

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Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Wongso¹,

Mahendra²,

Arnafia³

et al. 2022

Vaccines

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The coronavirus disease 2019 (COVID-19) has become a substantial threat to the international health sector and the global economy. As of 26 December 2021, the number of mortalities resulting from COVID-19 exceeded 5.3 million worldwide. The absence of an effective non-vaccine treatment has prompted the quest for prophylactic agents that can be used to combat COVID-19. This study presents the feasibility of chicken egg yolk antibody (IgY) anti-receptor-binding domain (RBD) spike SARS-CoV-2 as a strong candidate to neutralize the virus for application in passive immunization. For the purpose of preclinical studies, we radiolabeled IgY anti-RBD spike SARS-CoV-2 with radionuclide iodine-131. This allowed us to evaluate several biological characteristics of IgY in vitro, in vivo, and ex vivo. The preclinical data suggest that IgY anti-RBD spike SARS-CoV-2 could specifically bind to the SARS-CoV-2 antigens; however, little uptake was observed in normal cells (MRC-5) (<2%). Furthermore, the ex vivo biodistribution study revealed that IgY predominantly accumulated in the trachea of normal mice compared to other organs. We also found that IgY possessed a good safety profile when used as an intranasal agent. Taken together, we propose that IgY anti-RBD spike SARS-CoV-2 has the potential for application in passive immunization against COVID-19.

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Anti-HER2 monoclonal antibody based-radioimmunoconjugates: Assessment of the chelating agent influence

Cited by 3 publications

References 29 publications

Radioimmunotheranostic Pair Based on the Anti-HER2 Monoclonal Antibody: Influence of Chelating Agents and Radionuclides on Biological Properties

Radioimmunotheranostic Pair Based on the Anti-HER2 Monoclonal Antibody: Influence of Chelating Agents and Radionuclides on Biological Properties

An ultra-sensitive fluorescent Aptamer sensor based on 2D MOF for detection of HER2 in serum

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

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