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To directly radiolabel an anti-hepatoma mAb fragment HAb18 F(ab’)2 with 99mTc …


Biology Articles » Biophysics » Medical Biophysics » Direct technetium-99m labeling of anti-hepatoma monoclonal antibody fragment: a radioimmunoconjugate for hepatocellular carcinoma imaging » Introduction

Introduction
- Direct technetium-99m labeling of anti-hepatoma monoclonal antibody fragment: a radioimmunoconjugate for hepatocellular carcinoma imaging

The introduction of mAbs as targeting devices in nuclear medicine is well develo ped and many different antibodies which labeled with a variety of isotopes have been reported in cancer diagnosis. It seemed that 99mTc is the most popular radionuclide for nuclear medicine imaging because of its favorable physi cal characteristics, low cost, and ready availability. 99mTc labeled mAb fragments should be superior to other big molecule radioimmunoconjugates for u se in tumor R. A number of methods have been proposed for 99mTc labe ling proteins, and mAbs in particular. In general, these methodologies can be d ivided into two categories: indirect and direct methods[1]. In indirect method the protein was modified with a technetium binding ligand and then reacte d with a technetium complex. Several bifunctional chelating agents have been syn thesized and used, such as diethylenetriaminepenta acetic acid (DTPA)[2] , diamide dimercaptide N2S2 ligands, and hydrazino nicotinamide analog [3]. Although it is said that the indirect method can lead to loss of immuno reactivity. Joiris et al. have tested that the derivatization of antibody or fragment by iminothiolane does not split the protein and keeps the immunoreact ivity[4]. By direct method, 99mTc metal ion binds directly to endogenous donor groups on the antibody. The method is simple to perform and co mpatible with practical clinical use. However, direct labeling of mAbs with 99mTc was reported to be unstable due to non-specific binding (low and high-affinity)[5,6]but some reports suggest an improved labeling of proteins with 99mTc. In the Schwarz and Steinstrasser procedure, as modified by Mather and Ellison[7], disulide bridges in the mAb are reduc ed with 2-mercaptoethanol (2-ME). After purification, the resulting reduced an tibody can be stored frozen until required for use. Labeling is accomplished by addition of stannous ion from a bone- scanning kit and pertechnetate. In addit ion to using regular reducing agents, such as 2-ME, stannous ions[8]b orohydride[9], ascorbic acid[10], dithionite[11], or gl utathione[12]to generate sulphydryl groups, other peculiar approaches also appeared recently. Direct 99mTc labeling of mAbs were finis hed by reduction of antibodies using photoactivation and insoluble macromolecula r Sn() complex[13,14]. With the development of direct method, there ha ve been a few reports of successful use of this technique in colorectal, breast, and ovarian cancer imaging[15-17].
     
In this report, we describe a direct method for radiolabeling anti-hepatoma mon oclonal antibody fragment HAb 18F (ab’)2 with 99mTc. The stability and homogeneity of 99mc-HAb18 F(ab’)2 were evaluated. The biodis tribution and tumor localization in nude mice bearing a HHCC xenograft were studied.

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