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Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent.

Kirscher L, Deán-Ben XL, Scadeng M, Zaremba A, Zhang Q, Kober C, Fehm TF, Razansky D, Ntziachristos V, Stritzker J, Szalay AA - Theranostics (2015)

Bottom Line: In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models.Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography.At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

View Article: PubMed Central - PubMed

Affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany.

ABSTRACT
We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

No MeSH data available.


Related in: MedlinePlus

Evaluation of melanin amounts with MRI and optoacoustic imaging. Homogenized tissues of infected or PBS treated control A549 tumors analyzed by optoacoustic imaging at 700nm A) and MRI B) (n = 2-4). Correlation C) of MRI and MSOT signal intensities of the values in A) and B) (R² = 0,49).
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Figure 7: Evaluation of melanin amounts with MRI and optoacoustic imaging. Homogenized tissues of infected or PBS treated control A549 tumors analyzed by optoacoustic imaging at 700nm A) and MRI B) (n = 2-4). Correlation C) of MRI and MSOT signal intensities of the values in A) and B) (R² = 0,49).

Mentions: To further characterize the increasing melanin signal more quantitatively these tumors were homogenized and analyzed by MSOT and MRI (Fig. 7). In both cases, the received signals increased over time in the presence of dox for GLV-1h462 colonized tumor homogenates. The optoacoustic signal (Fig. 7A) of induced GLV-1h462 injected tumors was undistinguishable from the controls at the beginning of the dox induction and then increased steadily. Lysates of non-induced GLV-1h462 colonized tumors had optoacoustic signals that were in the range of the non-melanin producing controls even at the last time point. In contrast, lysates of GLV-1h460 colonized tumors contained much more melanin at the beginning of the experiment (2 days post start of the dox treatment). The somewhat higher melanin concentration at 18 days post dox treatment could be explained with the continuous production of melanin in those tumors.


Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent.

Kirscher L, Deán-Ben XL, Scadeng M, Zaremba A, Zhang Q, Kober C, Fehm TF, Razansky D, Ntziachristos V, Stritzker J, Szalay AA - Theranostics (2015)

Evaluation of melanin amounts with MRI and optoacoustic imaging. Homogenized tissues of infected or PBS treated control A549 tumors analyzed by optoacoustic imaging at 700nm A) and MRI B) (n = 2-4). Correlation C) of MRI and MSOT signal intensities of the values in A) and B) (R² = 0,49).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508495&req=5

Figure 7: Evaluation of melanin amounts with MRI and optoacoustic imaging. Homogenized tissues of infected or PBS treated control A549 tumors analyzed by optoacoustic imaging at 700nm A) and MRI B) (n = 2-4). Correlation C) of MRI and MSOT signal intensities of the values in A) and B) (R² = 0,49).
Mentions: To further characterize the increasing melanin signal more quantitatively these tumors were homogenized and analyzed by MSOT and MRI (Fig. 7). In both cases, the received signals increased over time in the presence of dox for GLV-1h462 colonized tumor homogenates. The optoacoustic signal (Fig. 7A) of induced GLV-1h462 injected tumors was undistinguishable from the controls at the beginning of the dox induction and then increased steadily. Lysates of non-induced GLV-1h462 colonized tumors had optoacoustic signals that were in the range of the non-melanin producing controls even at the last time point. In contrast, lysates of GLV-1h460 colonized tumors contained much more melanin at the beginning of the experiment (2 days post start of the dox treatment). The somewhat higher melanin concentration at 18 days post dox treatment could be explained with the continuous production of melanin in those tumors.

Bottom Line: In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models.Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography.At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

View Article: PubMed Central - PubMed

Affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany.

ABSTRACT
We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

No MeSH data available.


Related in: MedlinePlus