Tyrosinase as a multifunctional reporter gene for Photoacoustic/MRI/PET triple modality molecular imaging

Development of reporter genes for multimodality molecular imaging is highly important. In contrast to the conventional strategies which have focused on fusing several reporter genes together to serve as multimodal reporters, human tyrosinase (TYR) – the key enzyme in melanin production – was evaluated in this study as a stand-alone reporter gene for in vitro and in vivo photoacoustic imaging (PAI), magnetic resonance imaging (MRI) and positron emission tomography (PET). Human breast cancer cells MCF-7 transfected with a plasmid that encodes TYR (named as MCF-7-TYR) and non-transfected MCF-7 cells were used as positive and negative controls, respectively. Melanin targeted N-(2-(diethylamino)ethyl)-18F-5-fluoropicolinamide was used as a PET reporter probe. In vivo PAI/MRI/PET imaging studies showed that MCF-7-TYR tumors achieved significant higher signals and tumor-to-background contrasts than those of MCF-7 tumor. Our study demonstrates that TYR gene can be utilized as a multifunctional reporter gene for PAI/MRI/PET both in vitro and in vivo.

[1]  Lihong V. Wang,et al.  Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging , 2006, Nature Biotechnology.

[2]  Zhen Cheng,et al.  Harnessing the Power of Radionuclides for Optical Imaging: Cerenkov Luminescence Imaging , 2011, The Journal of Nuclear Medicine.

[3]  Martin Chalfie,et al.  GFP: lighting up life (Nobel Lecture). , 2009, Angewandte Chemie.

[4]  Junjie Yao,et al.  Photoacoustic microscopy of tyrosinase reporter gene in vivo. , 2011, Journal of biomedical optics.

[5]  Joachim Goedhart,et al.  Bright monomeric red fluorescent protein with an extended fluorescence lifetime , 2007, Nature Methods.

[6]  Johannes T. Heverhagen,et al.  In vitro MR imaging of regulated gene expression. , 2003, Radiology.

[7]  Zhen Cheng,et al.  Endoscopic imaging of Cerenkov luminescence , 2012, Biomedical optics express.

[8]  P. Farmer,et al.  Metal binding by melanins: studies of colloidal dihydroxyindole-melanin, and its complexation by Cu(II) and Zn(II) ions. , 2002, Journal of inorganic biochemistry.

[9]  Anan Abu Ubeid,et al.  Short-sequence oligopeptides with inhibitory activity against mushroom and human tyrosinase. , 2009, The Journal of investigative dermatology.

[10]  S. Arridge,et al.  Quantitative spectroscopic photoacoustic imaging: a review. , 2012, Journal of biomedical optics.

[11]  J. Simon,et al.  Characterization of the Fe(III)-binding site in Sepia eumelanin by resonance Raman confocal microspectroscopy. , 2004, Photochemistry and photobiology.

[12]  S. Gambhir,et al.  Noninvasive cell-tracking methods , 2011, Nature Reviews Clinical Oncology.

[13]  Efthimios Kaxiras,et al.  Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection. , 2008, Journal of biomedical optics.

[14]  Jung-Taek Oh,et al.  Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy. , 2006, Journal of biomedical optics.

[15]  I. Kawase,et al.  Glycine inhibits melanogenesis in vitro and causes hypopigmentation in vivo. , 2007, Biological & pharmaceutical bulletin.

[16]  Lihong V. Wang,et al.  Tyrosinase-catalyzed melanin as a contrast agent for photoacoustic tomography , 2011, BiOS.

[17]  C. Brennan,et al.  A Brain Tumor Molecular Imaging Strategy Using A New Triple-Modality MRI-Photoacoustic-Raman Nanoparticle , 2011, Nature Medicine.

[18]  Zhen Cheng,et al.  [99mTcOAADT]-(CH2)2-NEt2: a potential small-molecule single-photon emission computed tomography probe for imaging metastatic melanoma. , 2005, Cancer research.

[19]  P. Riley Molecules in focusMelanin , 1997 .

[20]  M. Pomper,et al.  Preclinical evaluation of an 131I-labeled benzamide for targeted radiotherapy of metastatic melanoma. , 2010, Cancer research.

[21]  S. Meyers,et al.  Intracranial Lesions with High Signal Intensity on T 1-weighted MR Images : Differential Diagnosis 1 , 2012 .

[22]  A. Casadevall,et al.  Radiolabeled melanin-binding peptides are safe and effective in treatment of human pigmented melanoma in a mouse model of disease. , 2006, Cancer biotherapy & radiopharmaceuticals.

[23]  K. Wakamatsu,et al.  Ion-exchange and adsorption of Fe(III) by Sepia melanin. , 2004, Pigment cell research.

[24]  Jan Grimm,et al.  Cerenkov luminescence imaging , 2015, Imaging Modalities for Biological and Preclinical Research: A Compendium, Volume 2.

[25]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[26]  J. Barrio,et al.  Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  Roger J. Zemp,et al.  Tyrosinase as a dual reporter gene for both photoacoustic and magnetic resonance imaging , 2011, Biomedical optics express.

[28]  S. Gambhir,et al.  64Cu-labeled alpha-melanocyte-stimulating hormone analog for microPET imaging of melanocortin 1 receptor expression. , 2007, Bioconjugate chemistry.

[29]  Loren Isom,et al.  Biodiesel Current and Future Perspectives , 2008 .

[30]  Simon R Cherry,et al.  Multimodality imaging: beyond PET/CT and SPECT/CT. , 2009, Seminars in nuclear medicine.

[31]  J. Simon,et al.  Current understanding of the binding sites, capacity, affinity, and biological significance of metals in melanin. , 2007, The journal of physical chemistry. B.

[32]  Zhen Cheng,et al.  Optical imaging of reporter gene expression using a positron-emission-tomography probe. , 2010, Journal of biomedical optics.

[33]  Yu Zhang,et al.  Fiber-laser-based photoacoustic microscopy and melanoma cell detection. , 2011, Journal of biomedical optics.

[34]  Zhen Cheng,et al.  Radiation-luminescence-excited quantum dots for in vivo multiplexed optical imaging. , 2010, Small.

[35]  J. Simon,et al.  Binding of Metal Ions to Melanin and Their Effects on the Aerobic Reactivity¶ , 2004, Photochemistry and photobiology.

[36]  Zhen Cheng,et al.  Proof-of-Concept Study of Monitoring Cancer Drug Therapy with Cerenkov Luminescence Imaging , 2012, The Journal of Nuclear Medicine.

[37]  R. Tsien,et al.  Imaging Tri-Fusion Multimodality Reporter Gene Expression in Living Subjects , 2004, Cancer Research.

[38]  P. Beard Biomedical photoacoustic imaging , 2011, Interface Focus.

[39]  Ronald G Blasberg,et al.  Molecular-genetic imaging: current and future perspectives. , 2003, The Journal of clinical investigation.

[40]  R. McLendon,et al.  Intracerebral malignant melanoma: high-field-strength MR imaging. , 1987, Radiology.

[41]  Zhen Cheng,et al.  Development of 18F-labeled picolinamide probes for PET imaging of malignant melanoma. , 2013, Journal of medicinal chemistry.

[42]  S Subramani,et al.  Firefly luciferase as a tool in molecular and cell biology. , 1988, Analytical biochemistry.

[43]  Lei Xing,et al.  Intraoperative Imaging of Tumors Using Cerenkov Luminescence Endoscopy: A Feasibility Experimental Study , 2012, The Journal of Nuclear Medicine.

[44]  A. Brożyna,et al.  Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy , 2008, International journal of cancer.

[45]  S. Gambhir,et al.  Melanin-Targeted Preclinical PET Imaging of Melanoma Metastasis , 2009, Journal of Nuclear Medicine.

[46]  E. Dadachova,et al.  In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma. , 2011, Cancer biotherapy & radiopharmaceuticals.

[47]  Tyler Harrison,et al.  In vivo imaging of inducible tyrosinase gene expression with an ultrasound array-based photoacoustic system , 2012, Photonics West - Biomedical Optics.

[48]  S. Gambhir,et al.  Small-Animal PET Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with Site-Specific 18F-Labeled Protein Scaffold Molecules , 2008, Journal of Nuclear Medicine.

[49]  R. Blasberg,et al.  A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[50]  Ashutosh Kumar Singh,et al.  Noninvasive Molecular Neuroimaging Using Reporter Genes: Part II, Experimental, Current, and Future Applications , 2008, American Journal of Neuroradiology.

[51]  Sanjiv S. Gambhir,et al.  Molecular Optical Imaging with Radioactive Probes , 2010, PloS one.

[52]  Tyler Harrison,et al.  Photoacoustic imaging of gene expression using tyrosinase as a reporter gene , 2011, BiOS.

[53]  F. Figge Melanin , 1939, The New England journal of medicine.

[54]  J P Kassirer,et al.  What is a differential diagnosis? , 1990, Hospital practice.

[55]  R Weissleder,et al.  MR imaging and scintigraphy of gene expression through melanin induction. , 1997, Radiology.

[56]  Ralph Weissleder,et al.  Single reporter for targeted multimodal in vivo imaging. , 2012, Journal of the American Chemical Society.