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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
- 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 RⅡ.
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. 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)
, diamide dimercaptide N2S2 ligands, and
hydrazino nicotinamide analog . 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. 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
some reports suggest an improved labeling of proteins with 99mTc.
In the Schwarz and Steinstrasser procedure, as modified by Mather
and Ellison, 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，b
orohydride, ascorbic acid, dithionite,
or gl utathioneto 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(Ⅱ)
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].
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 99mＴc-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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