Direct Labeling of Monoclonal Antibodies and Antibody Fragments with <sup>188</sup>Re Using a Weak Competing Ligand

Ferro‐Flores, Guillermina; Hashimoto, Kazuhito

doi:10.1524/ract.1997.79.1.63

Cited by 11 publications

(3 citation statements)

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“…Increased effort has been made to label mAbs with rhenium-188, samarium-153, yttrium-90, and lutetium-177 because of their potential role in the radioimmunotherapy of cancer ( − ). However, the radiolabeling of mAbs or F(ab') 2 fragments with Sm-153 by combination of avidin−biotin strategy has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Pharmacokinetics of Samarium(III)-153-Labeled DTPA-bis-Biotin. Characterization and Theoretical Studies of the Samarium(III)-152 Conjugate

et al. 1999

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The complex(153)Sm(III)DTPA-bis-biotin was prepared with a 99% radiochemical purity and a specific activity of 370 MBq/mg employing a molar ratio of DTPA-bis-biotin/Sm from 2 to 4 at pH 8.0. In vitro studies demonstrated that the complex is stable after dilution in saline and in human serum. Avidity of labeled biotin for avidin was not affected by the labeling procedure. Pharmacokinetic data of (153)Sm(III)DTPA-bis-biotin in normal mice showed that blood clearance is biexponential during the time interval from 0 to 24 h and that 3 h postinjection 92 +/- 4.32% of the dose is eliminated in the urine. To have further evidence which could sustain that (153)Sm(III)DTPA-bis-biotin is stable in solution as a real coordination complex, (152)Sm(III)DTPA-bis-biotin was obtained in macroscopic quantities and its characterization was done by IR, TGA, and conductivity measurements. The results indicated that the complex was chemically pure, where the Sm(3+) ion is neutralized by three carboxylate groups of the DTPA-bis-biotin ligand and coordinated to it. Using the Force Field method followed by ab initio calculations, the DTPA-bis-biotin and the Sm(III)DTPA-bis-biotin molecules were done. Accordingly, the coordination sphere of Sm(III) was totally satisfied with nitrogen and oxygen donors; the best coordination number was 9. The conformation geometry of both compounds is presented.

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Section: Introductionmentioning

confidence: 99%

Preparation and Pharmacokinetics of Samarium(III)-153-Labeled DTPA-bis-Biotin. Characterization and Theoretical Studies of the Samarium(III)-152 Conjugate

et al. 1999

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“…Recently it has been shown that 90 Y labelled Mab fragments are effective at curing small tumors with relatively few side effects [162]. On the other hand, increased effort has been made to label Mabs with rhenium-188, because of its potential role in the RIT of cancer and the recent availability of 188 Re from a W-188/Re-188 generator [163,164].…”

Section: Monoclonal Antibodies and Their Fragmentsmentioning

confidence: 99%

Preface

Ercan¹,

Çağlar²

2000

CPD

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A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In order to destroy the diseased tissues radionuclides with high linear energy transfer (LET) such as beta, alpha, Auger or low energy conversion electron emitters are needed. The range of beta particles is in mm's so they are effective for large tumors. The range of alpha particles is short, only a few cell diameters. Thus, they are effective in treating circulating malignant cells and micrometastases. The range of Auger and conversion electrons is <0.1 micro m. They are very effective in cell killing when they are carried across cell membrane into the nucleus to damage DNA. Appropriate ions, molecules and particles are labelled with such radionuclides and used as radiopharmaceuticals in many different applications. For an effective dose to be delivered high target to non target ratios must be attained. Monoclonal antibodies to specific antigens expressed on tumor cells have been developed to increase the uptake by malignant tissues by specific accumulation. Radiolabelled peptides such as somatostatin, small molecules such as metaiodo-benzylguanidine (MIBG) and many different nano-and micro-particles have been investigated. The effectiveness of therapy can be increased by direct locoregional administration of the radiopharmaceutical. This way the radiation effects are confined locally and the normal tissues are spared from radiation effects. In this review article selection criteria and characteristics of radionuclides and carrier ions, molecules and particles for various therapeutic applications will be discussed, including mainly the recent developments.

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“…Oliver e colaboradores usaram 1,67 mg de SnF 2 (correspondente a 1,26 mg de Sn 2+ ) e obtiveram um bom rendimento de marcação com uma atividade de 188 Re de 1,5 -1,9 GBq (40,5 -51,3 mCi) (Oliver et al, 2005). (Perera et al, 2003;Ferro-Flores & Hashimoto, 1997;Kodina et al, 2005). O efeito da massa de tartarato foi estudado e os resultados encontrados estão demonstrados na FIG.…”

Section: Marcação Direta: Variáveis E Análise Radioquímica Usando Cp unclassified

Estudo comparativo da marcação do anticorpo anti-CD20 com 188Re

Dias¹

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Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m (99m Tc) and rhenium-188 (188 Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis (99m Tc: T 1/2 = 6 h, γ radiation = 140 keV) and therapy (188 Re: T 1/2 = 17 h, maximum β − energy = 2.12 MeV) and to their availability in the form of 99 Mo/ 99m Tc and 188 W/ 188 Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with 188 Re using two techniques: the direct labeling method [ 188 Re(V)] and the labeling method via the carbonyl nucleus [ 188 Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with 188 Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both 99m Tc and 188 Re were employed through 2 different procedures: (1) labeling of intact RTX with 99m Tc(I) and (2) reduced RTX (RTX red) labeled with 99m Tc(I)/ 188 Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method via carbonyl group, the results showed that the-SH groups of RTX red are a possible way of labeling. The formulation of 99m Tc(I)-RTX red was faster than 188 Re(I)-RTX red , that on the other hand showed better stability in human plasma and no transquelation in the cysteine or histidine challenge studies. Both compounds showed good binding affinity and a biodistribution in mice bearing tumor compatible with the normal mAb distribution and a reasonable tumor uptake proving the efficiency of the labeling and the potential clinical use. 5.4.4 Estudos in vivo: 99m Tc/ 188 Re(CO) 3-RTX red .

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Direct Labeling of Monoclonal Antibodies and Antibody Fragments with ¹⁸⁸Re Using a Weak Competing Ligand

Cited by 11 publications

References 10 publications

Preparation and Pharmacokinetics of Samarium(III)-153-Labeled DTPA-bis-Biotin. Characterization and Theoretical Studies of the Samarium(III)-152 Conjugate

Preparation and Pharmacokinetics of Samarium(III)-153-Labeled DTPA-bis-Biotin. Characterization and Theoretical Studies of the Samarium(III)-152 Conjugate

Preface

Estudo comparativo da marcação do anticorpo anti-CD20 com 188Re

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Direct Labeling of Monoclonal Antibodies and Antibody Fragments with 188Re Using a Weak Competing Ligand

Cited by 11 publications

References 10 publications

Preparation and Pharmacokinetics of Samarium(III)-153-Labeled DTPA-bis-Biotin. Characterization and Theoretical Studies of the Samarium(III)-152 Conjugate

Preparation and Pharmacokinetics of Samarium(III)-153-Labeled DTPA-bis-Biotin. Characterization and Theoretical Studies of the Samarium(III)-152 Conjugate

Preface

Estudo comparativo da marcação do anticorpo anti-CD20 com 188Re

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Direct Labeling of Monoclonal Antibodies and Antibody Fragments with ¹⁸⁸Re Using a Weak Competing Ligand