Physics And Chemistry Basis Of Biotechnology - De Cuyper - tiera.ru

Radioactive microspheres for medical applications
The radiopharmaceutical 99m Tc-sulfur colloid is also used for gastrointestinal blood loss
studies, for the preparation of a 99m Tc-labeled egg sandwich for gastric emptying studies
[39], and for the determination of oesophageal transit and gastro-oesophageal reflux.
For colonic transit studies, radioisotopes with a half-life longer than 99mTc are more
appropriate, and 111 In-labeled ion exchange resins, but also 131l-cellulose are utilised
[96]. Latex-particles of 2.5 µm size and labelled with 99m
Tc have also been shown to
give excellent abdominal images [97]. In all these gastrointestinal transit time studies,
the size of the radiolabelled microspheres does not influence the measured times.
Radiolabelled liposomes, another diagnostic class of radioactive particles, has been
used for tumour imaging since 1977. In order to prolong the blood residence time and
maximise tumour uptake, neutral, positively and negatively charged small unilamellar
vesicles (= SUV's) of 65 nm encapsulating 111In were made and their biodistribution
measured in mice [98]. The highest uptake of 18.5% of injected dose per gram of
tumour was measured with the neutral liposomes. A further attempt to minimise the
67 111
high blood-background radioactivity levels was to inject Ga- or In-labeled
liposomes containing biotin groups on their surface and then chasing the non-tumour
bound liposomes 2 hours later with avidin [99]. This chase removed the unbound
liposomes effectively from the circulation and the blood concentration of the
radioactive liposomes dropped to a tumour-to-blood ratio of about 15 to 1 shortly after
the avidin chase. The avidin-biotin-liposome conglomerates accumulated in the liver
and increased the liver activity about 2.5 fold.
Radiolabelled microspheres can also be used to image cancer lesions. An interesting
application is the use of PLA-microspheres labelled with 131T-iopanoic acid derivatives
for the imaging of liver tumours [44]. The normal liver parenchyma lined with Kupffer
cells takes up the microspheres, but the cancer lesions do not possess fixed
macrophages and therefore exclude the radioactive microspheres, showing the focal
lesions as defects. The recently introduced 99mTc-PLA microspheres which were
radiolabelled in a SnCl2-containing kit could be used for the same application [100],
although the stability described as "more than 80% bound after 6 hours" is not optimal
yet.
The in vivo faith of microspheres after intra-arterial catheter-mediated delivery
through a porous balloon to a rabbit's femoral artery has been investigated with
radioactive 141 Ce-microspheres [ 101]. Although only 0.14% to 0.16% of the
microspheres were delivered to the vessel wall, an average of 92% of these
microspheres was still present 7 days later. In addition, much higher amounts of the
microspheres were found in the periadventitia (the vessel's "outside") and the overlying
musculature and are believed to be caused by the increase of vaso vasora present in
atherosclerotic patients. Although the targeted amounts of microspheres are small, they
can lead to drug concentrations a few hundred times higher than the serum
concentrations, allowing for effective restenosis therapy with microspheres containing
cytostatic or antiproliferative agents, especially from the periadventitia side.
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