Radiolabeling and biodistribution of monoclonal antibody (MAb) anti-CD20 with iodine-131

Abstract

Radioactive isotopes of iodine, mainly iodine-131 have been broadly used in many monoclonal antibody radioiodination settings, employing different methods. In this study, using a Chloramine-T procedure, the influence of incubation time, CT mass, and Ab/activity ratio on the radiochemical yield of the anti-CD20 antibody labeled with iodine-131 was observed. Radiochemical yield was > 97 %, employing different Chloramine-T masses, independently of incubation time. Radiochemical purity was above 99 % after purification of the labeled compound. The relationship between Ab mass and radioactivity was tested and no difference was observed when 90.6 MBq (2.45mCi) of activity was incorporated in the Ab-mass range studied. Biodistribution study in normal Swiss mice showed higher uptake by the liver and intestines. Low thyroid uptake indicated a suitable in vivo stability. Slight blood uptake was considered a result of circulating radioactivity in normal organs and tissues. A favorable biological distribution of 131I-anti-CD20 suggests this radiopharmaceutical may be effectively used in the therapy of Non Hodgkin Lymphoma.<br>Radioisótopos de iodo, principalmente iodo-131 foram muito utilizados em vários procedimentos de marcação de anticorpos monoclonais usando diferentes métodos tais como o de Cloramina-T(CT). Neste estudo, observamos a influência de tempo de incubação, massa de CT, relação anticorpo/actividade na pureza radioquímica no anticorpo anti-CD20 marcado com iodo-131. A pureza radioquímica foi superior a 97% quando massas diferentes de CT foram utilizadas independentes do tempo de incubação. A pureza radioquímica superior a 99% após a purificação do composto radiomarcado. Todavia, a relação entre anticorpo/atividade foi determinada e nenhuma diferencia foi observada quando 90,6 MBq (2.45 mCi) foram incorporados a 10, 25, 50 ou 100 µg de Ac exceto uma pequena redução em 10 µg. O estudo de distribuição biológica em camundongo Swiss normais demonstrou captação elevada no fígado e nos intestinos. A baixa captação na tireóide atesta que o produto apresenta estabilidade in vivo satisfatória. Traços de atividade apresentado pelo sangue podem ser considerados como resultado de actividade circulante nos órgãos normais. A distribuição biológica favorável do composto marcado é uma indicação forte à aplicabilidade do radiofármaco na terapia de linfomas não-Hodgkins (LNH)

Synthesis and Preclinical Evaluation of177Lu-CHX-A”-DTPA-Rituximab as a Radioimmunotherapeutic Agent for Non-Hodgkin's Lymphoma

“…Comparison of results of biodistribution studies of 177 Lu-CHX-A''-DTPA-Rituximab with 131 I Rituximab and 90 Y Rituximab in normal mice showed similar uptake and clearance pattern in the organs. 5,45,46 However, a direct comparison of biodistribution studies of 177 Lu-CHX-A''-DTPA-Rituximab with the values reported for 131 I Rituximab in tumor-bearing animals is not possible due to the different routes of administration of the radiolabeled conjugates. 47 Favorable results obtained in radiochemical and biological evaluation studies warrant further studies such as dosimetry studies for translation of 177 Lu-CHX-A''-DTPARituximab to a clinical setup.…”

Antibody biodistribution coefficients

“…Twenty-one different mouse tissue distribution studies from published references other than the ones used to develop the mouse training data set, with various kinds of mAbs and ADC, in various animal models and with diverse radiolabels, were used to build the mouse validation data set. [13][14][15][20][21][22][23][24][25][26][27][28] Details about the individual biodistribution studies are provided in Table S2. Based on Equation 1, using the plasma mAb concentration and ABC values, expected tissue concentrations were calculated for each tissue.…”

Labeling of the Recombinant Streptokinase Using Iodine-131 as a New Thrombolytic Agent

“…There are many methods of protein labeling with radioiodine, mostly oxidative reaction. Iodine-131 have been proven to be appropriated for labeling both small and large bio-molecules, protein or peptides, well known chemistry, availability easier, and low cost [7].…”