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 percent, employing different Chloramine-T masses, independently of incubation time. Radiochemical purity was above 99 percent 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.
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 por cento quando massas diferentes de CT foram utilizadas independentes do tempo de incubação. A pureza radioquímica superior a 99 por cento 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 æg de Ac exceto uma pequena redução em 10 æg. 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).
ABSTRACT
The labeling with 177Lu and quality control procedures to produced DOTA (1,4,7,10-N,N´,N´´,N´´´, tetraazaciclododecane tetraacetic acid) coupled octreotate labeled peptide was evaluated. The labeling was performed using 30µg of DOTA-Tyr3-octreotate and 500 and 1110 MBq of 177Lu, buffered with sodium acetate/acetic acid 0.4M pH 4.5 for 20 minutes at 100ºC. The radiochemical purity was determined by ITLC na HPLC. Biological distribution studies were performed on Nude mices with tumours (AR42J rat pancreatic tumour cells) by invasive method. The stability of the 177Lu-DOTA-Tyr3-octreotate was followed by 7 days, and in both labeling procedures, the radiochemical purity were superior than 98 percent. Biodistribution studies showed fast blood clearance and the kidneys were the critical organs. The uptake in tumour were significant after 24 hours and the labeled peptide showed high in vivo stability.