Nanoparticles as Contrast Agents for Optoacoustic Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 113

figure 5.3 Optoacoustic image of a mouse ear showing post injection formation of
tyrosinase-derived melanin on the background of hemoglobin in the tissue microvascul-
ture. Inset shows a photograph of the OA image area outlined with a gray dashed square.
melanin production area is outlined with dashed circles on both, the OA image and the
photograph. (Adapted with permission from Ref. [55] sPIe-International society for
Optical engineers).
In addition to imaging and diagnostics, melanin was shown to be a suitable target
for laser-induced thermotherapy and enhanced oncolytic viral therapy. Regarding
the latter, stritzker et al . [54] provided evidence that gene-evoked production of
melanin could be used as a therapeutic and diagnostic mediator, as exemplified by
insertion of only one or two genes into the genome of an oncolytic vaccinia virus
strain. such modified viruses resulted in a new class of theranostic agents. Oncolytic
viruses are characterized by their largely tumor cell-specific replication, resulting in
tumor cell lysis and efficient tumor regression. Tumor selectivity is an inherent
property of viruses such as Newcastle disease virus, parvovirus, and vaccinia virus
[54]. These could be further enhanced, for example, by deletion of viral genes,
which are dispensable in malignant cells, or by production of surface receptors that
bind ligands that are highly expressed on tumor cells [56]. The oncolytic vaccinia
virus strain gLV-1h68 serves as the backbone for the insertion of key genes in
melanogenesis genes into tumor cells. Being inserted, the genes might be rendered
“visible” as a result of melanin overproduction by optical as well as OA imaging and
might facilitate therapy and use the produced melanin as an additional theranostic
mediator [55].
The oncolytic virus-mediated production of melanin and its optical absorption in
the NIR enable the optical (and OA) imaging of tumors and metastases. It was found
[54] that pellets of cells infected with various melanin-rVAcV strains showed OA
signals in the NIR range that were equivalent to optical absorption up to 2 cm −1 .
A significant increase in melanin production in a cell culture is related to the darker
color of eumelanin in cells and tissues and, as a result, serves as a better OA contrast.
These values are an order of magnitude above the 0.3-0.5 cm −1 tissue optical
absorption in NIR and are comparable with the 2 cm −1 absorption of whole blood,
thus ensuring sufficient signal-to-background ratio. In combination with multispectral