Photoacoustic microscopy of tyrosinase reporter gene in vivo

Krumholz, Arie; VanVickle-Chavez, Sarah J.; Yao, Junjie; Fleming, Timothy P.; Gillanders, William E.; Wang, Lihong V.

doi:10.1117/1.3606568

Cited by 71 publications

(71 citation statements)

References 24 publications

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“…Here, the oncolytic vaccinia virus strain GLV-1h68 served as backbone for the insertion of key genes in melanogenesis. We speculated that introduction of melanogenesis into tumor cells might render them visible as a result of melanin overproduction by optical as well as optoacoustic imaging (6) and might facilitate therapy. Furthermore, it is well known that melanotic melanomas generate high signal on T1-weighted magnetic resonance images (7,8), probably as a result of trapping of paramagnetic transition metal ions (9).…”

mentioning

confidence: 99%

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer

Stritzker

Kirscher

Scadeng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

111

142

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We reported earlier the delivery of antiangiogenic single chain antibodies by using oncolytic vaccinia virus strains to enhance their therapeutic efficacy. Here, we provide evidence that gene-evoked production of melanin can 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. We found that produced melanin is an excellent reporter for optical imaging without addition of substrate. Melanin production also facilitated deep tissue optoacoustic imaging as well as MRI. In addition, melanin was shown to be a suitable target for laser-induced thermotherapy and enhanced oncolytic viral therapy. In conclusion, melanin as a mediator for thermotherapy and reporter for different imaging modalities may soon become a versatile alternative to replace fluorescent proteins also in other biological systems. After ongoing extensive preclinical studies, melanin overproducing oncolytic virus strains might be used in clinical trials in patients with cancer.

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mentioning

confidence: 99%

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer

Stritzker

Kirscher

Scadeng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

111

142

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“…© As a major implementation of photoacoustic tomography, optical-resolution photoacoustic microscopy (OR-PAM) has been proven capable of anatomical, chemical, functional, and metabolic imaging. [1][2][3][4][5][6][7][8] OR-PAM provides a capillary-level spatial resolution by tightly focusing the laser beam at depths within the optical diffusion limit (∼1 mm in the skin).…”

mentioning

confidence: 99%

Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror

et al. 2012

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“…For example, tyrosinase converts tyrosine into eumelanin, an endogenous tissue chromophore that absorbs in the visible and near-infrared part of the spectrum. This has been used to visualize otherwise transparent tumor cells using photoacoustic imaging in vivo [4,5]. Another enzymatic approach is the genetic expression of β-galactosidase, an Escherichia coli enzyme involved in the metabolism of lactose, from the lacZ gene.…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization of genetically expressed absorbing proteins using photoacoustic spectroscopy

Laufer

Jathoul

Pulé³

et al. 2013

Biomed. Opt. Express

104

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Genetically expressed fluorescent proteins have been shown to provide photoacoustic contrast. However, they can be limited by low photoacoustic generation efficiency and low optical absorption at red and near infrared wavelengths, thus limiting their usefulness in mammalian small animal models. In addition, many fluorescent proteins exhibit low photostability due to photobleaching and transient absorption effects. In this study, we explore these issues by synthesizing and characterizing a range of commonly used fluorescent proteins (dsRed, mCherry, mNeptune, mRaspberry, AQ143, E2 Crimson) and novel non-fluorescent chromoproteins (aeCP597 and cjBlue and a non-fluorescent mutant of E2 Crimson). The photoacoustic spectra, photoacoustic generation efficiency and photostability of each fluorescent protein and chromoprotein were measured. Compared to the fluorescent proteins, the chromoproteins were found to exhibit higher photoacoustic generation efficiency due to the absence of radiative relaxation and ground state depopulation, and significantly higher photostability. The feasibility of converting an existing fluorescent protein into a non-fluorescent chromoprotein via mutagenesis was also demonstrated. The chromoprotein mutant exhibited greater photoacoustic signal generation efficiency and better agreement between the photoacoustic and the specific extinction coefficient spectra than the original fluorescent protein. Lastly, the genetic expression of a chromoprotein in mammalian cells was demonstrated. This study suggests that chromoproteins may have potential for providing genetically encoded photoacoustic contrast.

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Photoacoustic microscopy of tyrosinase reporter gene in vivo

Cited by 71 publications

References 24 publications

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer

Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror

In vitro characterization of genetically expressed absorbing proteins using photoacoustic spectroscopy

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