In vivo macroscopic HPD fluorescence reflectance imaging on small animals bearing surface ARO/NPA tumor

Recently multimodal imaging systems have been devised because the combination of different imaging modalities results in the complementarity and integration of the techniques and in a consequent improvement of the diagnostic capabilities of the multimodal system with respect to each separate imaging modality. We developed a simple and reliable HematoPorphyrin (HP) mediated Fluorescence Reflectance Imaging (FRI) system that allows for in vivo real time imaging of surface tumors with a large field of view. The tumor cells are anaplastic human thyroid carcinoma-derived ARO cells, or human papillary thyroid carcinoma-derived NPA cells. Our measurements show that the optical contrast of the tumor region image is increased by a simple digital subtraction of the background fluorescence and that HP fluorescence emissivity of ARO tumors is about 2 times greater than that of NPA tumors, and about 4 times greater than that of healthy tissues. This is also confirmed by spectroscopic measurements on histological sections of tumor and healthy tissues. It was shown also the capability of this system to distinguish the tumor type on the basis of the different intensity of the fluorescence emission, probably related to the malignancy degree. The features of this system are complementary with those ones of a pixel radionuclide detection system, which allows for relatively time expensive, narrow field of view measurements, and applicability to tumors also deeply imbedded in tissues. The fluorescence detection could be used as a large scale and quick analysis tool and could be followed by narrow field, higher resolution radionuclide measurements on previously determined highly fluorescent regions.

[1]  Giovanni Mettivier,et al.  Preliminary tests of a prototype system for optical and radionuclide imaging in small animals , 2002 .

[2]  S. Gambhir,et al.  Optical imaging of Renilla luciferase reporter gene expression in living mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Petras Juzenas,et al.  Noninvasive fluorescence excitation spectroscopy during application of 5-aminolevulinic acid in vivo , 2002, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[4]  Vasilis Ntziachristos,et al.  Shedding light onto live molecular targets , 2003, Nature Medicine.

[5]  Vasilis Ntziachristos,et al.  Would near-infrared fluorescence signals propagate through large human organs for clinical studies? , 2002, Optics letters.

[6]  Arjun G Yodh,et al.  Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model. , 2003, Journal of biomedical optics.

[7]  R Weissleder,et al.  In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. , 2000, Cancer research.

[8]  A H Kaye,et al.  Selective uptake of hematoporphyrin derivative into human cerebral glioma. , 1990, Neurosurgery.

[9]  G Morstyn,et al.  Uptake of hematoporphyrin derivative by normal and malignant cells: effect of serum, pH, temperature, and cell size. , 1985, Cancer research.

[10]  Johan Moan,et al.  pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer. , 2003, Cancer letters.

[11]  S. Taketani,et al.  Mechanisms involved in the cellular uptake of hematoporphyrin by rat hepatoma cells. , 1988, Journal of biochemistry.

[12]  L. Celentano,et al.  Experimental study on in vivo optical and radionuclide imaging in small animals , 2003, 2003 IEEE Nuclear Science Symposium. Conference Record (IEEE Cat. No.03CH37515).

[13]  W. Semmler,et al.  Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands , 2001, Nature Biotechnology.

[14]  Bruce J. Tromberg,et al.  Congruent MRI and Near-infrared Spectroscopy for Functional and Structural Imaging of Tumors , 2002, Technology in cancer research & treatment.

[15]  M W Berns,et al.  In vitro photosensitization I. Cellular uptake and subcellular localization of mono‐L‐aspartyl chlorin e6, chloro‐aluminum sulfonated phthalocyanine, and photofrin II , 1989, Lasers in surgery and medicine.

[16]  Ralph Weissleder,et al.  In vivo molecular target assessment of matrix metalloproteinase inhibition , 2001, Nature Medicine.

[17]  R. Weissleder,et al.  Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging , 2002, European Radiology.

[18]  R Cubeddu,et al.  Study of porphyrin fluorescence in tissue samples of tumour-bearing mice. , 1995, Journal of photochemistry and photobiology. B, Biology.

[19]  Meng Yang,et al.  Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. S. Sobolev,et al.  Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency , 2000, Immunology and cell biology.

[21]  H Jiang,et al.  Combined optical and fluorescence imaging for breast cancer detection and diagnosis. , 2000, Critical reviews in biomedical engineering.

[22]  R. Weissleder,et al.  In vivo imaging of tumors with protease-activated near-infrared fluorescent probes , 1999, Nature Biotechnology.

[23]  H. Shimada,et al.  Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Seema Gupta,et al.  Cellular uptake, localization and photodynamic effects of haematoporphyrin derivative in human glioma and squamous carcinoma cell lines. , 2003, Journal of photochemistry and photobiology. B, Biology.

[25]  Daniel C Sullivan,et al.  Challenges and Opportunities for In Vivo Imaging in Oncology , 2002, Technology in cancer research & treatment.

[26]  D. Kessel Components of hematoporphyrin derivatives and their tumor-localizing capacity. , 1982, Cancer research.

[27]  S. Achilefu,et al.  Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging. , 2000, Investigative radiology.

[28]  Victor X D Yang,et al.  A multispectral fluorescence imaging system: Design and initial clinical tests in intra‐operative Photofrin‐photodynamic therapy of brain tumors , 2003, Lasers in surgery and medicine.

[29]  Jolanta Saczko,et al.  Uptake of photofrin II, a photosensitizer used in photodynamic therapy, by tumour cells in vitro. , 2003, Acta biochimica Polonica.

[30]  K Svanberg,et al.  Clinical multi-colour fluorescence imaging of malignant tumours - initial experience , 1998, Acta radiologica.

[31]  U. Mahmood,et al.  Near infrared optical applications in molecular imaging , 2004, IEEE Engineering in Medicine and Biology Magazine.

[32]  G. Jori,et al.  Temperature-induced changes in fluorescence properties as a probe of porphyrin microenvironment in lipid membranes. 2. The partition of hematoporphyrin and protoporphyrin in mitochondria. , 1995, European journal of biochemistry.