<sup>99m</sup>Tc-MAG3-Aptamer
for Imaging Human Tumors
Associated with High Level of Matrix Metalloprotease‑9
- Publication date
- Publisher
Abstract
The human matrix metalloprotease 9 (hMMP-9) is involved
in many
physiological processes such as tissue remodeling. Its overexpression
in tumors promotes the release of cancer cells thus contributing to
tumor metastasis. It is a relevant marker of malignant tumors. We
selected an RNA aptamer containing 2′-fluoro, pyrimidine ribonucleosides,
that exhibits a strong affinity for hMMP-9 (<i>K</i><sub>d</sub> = 20 nM) and that discriminates other human MMPs: no binding
was detected to either hMMP-2 or -7. Investigating the binding properties
of different MMP-9 aptamer variants by surface plasmon resonance allowed
the determination of recognition elements. As a result, a truncated
aptamer, 36 nucleotides long, was made fully resistant to nuclease
following the substitution of every purine ribonucleoside residue
by 2′-<i>O</i>-methyl analogues and was conjugated
to <i>S</i>-acetylmercaptoacetyltriglycine for imaging purposes.
The resulting modified aptamer retained the binding properties of
the originally selected sequence. Following <sup>99m</sup>Tc labeling,
this aptamer was used for ex vivo imaging slices of human brain tumors.
We were able to specifically detect the presence of hMMP-9 in such
tissues