The aim of this study was to determine whether contrast-enhanced micro-computed tomography can be used for non-invasive imaging of the early-stage changes in the vasculature of tumours that have been treated with photodynamic therapy (PDT). The subjects used were C3H mice with an RIF-1 tumour implanted subcutaneously and allowed to grow for 3 weeks prior to treatment. The experimental groups were PDT-treated (150 J/cm 2 and 50 J/cm 2 ) and control (150 J/cm 2 light-only and untreated). The laser light exposure was performed at 15 - 30 minutes after the administration of the photosensitizer (BPD-MA). The contrast-enhanced micro-computed tomography imaging procedure consisted of eight-second scans taking place before treatment and up to 24 hours after treatment. The 150 J/cm 2 PDT group showed a significant increase in the ratio of blood volume to tumour volume at 2, 8 and 24 hours after treatment when compared to pre-treatment measurements (p < 0.01). The observed increase in the blood volume to tumour volume at the later time points corresponds to a decrease in epithelial coverage on immunohistochemical stained (CD31) slides for the 150 J/cm 2 PDT group at 24 hours after treatment. This preliminary study indicates that micro-CT can detect compromised vasculature in tumours treated with high-fluence photodynamic therapy as early as 2 hours post treatment.
Richter, A.M., Jain, A.K., Canaan, A.J., et al. (1992) Photosensitizing efficiency of two regioisomers of the ben zoporphyrin derivative monoacid ring A (BPD-MA). Bio chemical Pharmacology, 43, 2349-2358. doi:10.1016/0006-2952(92)90313-8
Ichikawa, K., Takeuchi, Y., Yonezawa, S., et al. (2004) Antiangiogenic photodynamic therapy (PDT) using Visu dyne causes effective suppression of tumor growth. Cancer Letters, 205, 39-48. doi:10.1016/j.canlet.2003.10.001
Chen, B., Pogue, B.W., Goodwin, I.A., et al. (2003) Blood flow dynamics after photodynamic therapy with vertepor fin in the RIF-1 tumor. Radiation Research, 160, 452-459. doi:10.1667/RR3059
Chen, B., Xu, Y., Roskams, T., et al. (2001) Efficacy of antitumoral photodynamic therapy with hypericin: Relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model. International Journal of Cancer, 93, 275-282. doi:10.1002/ijc.1324
Osaki, T., Takagi, S., Hoshino, Y., et al. (2007) Antitumor effects and blood flow dynamics after photodynamic therapy using benzoporphyrin derivative monoacid ring A in KLN205 and LM8 mouse tumor models. Cancer Letters, 248, 47-57. doi:10.1016/j.canlet.2006.05.021
Banihashemi, B., Vlad, R., Debeljevic, B., et al. (2008) Ultrasound imaging of apoptosis in tumor response: Novel preclinical monitoring of photodynamic therapy effects. Cancer Research, 68, 8590-8596. doi:10.1158/0008-5472.CAN-08-0006
Burch, S., London, C., Seguin, B., et al. (2009) Treatment of canine osseous tumors with photodynamic therapy: A pilot study. Clinical Orthopaedics and Related Research, 467, 1028-1034. doi:10.1007/s11999-008-0678-5
Fercher, A.F., Drexler, W., Hitzenberger, C.K., et al. (2003) Optical coherence tomography—Principles and applications. Reports on Progress in Physics, 66, 239-303. doi:10.1088/0034-4885/66/2/204
Celli, J.P., Spring, B.Q., Rizvi, I., et al. (2010) Imaging and photodynamic therapy: Mechanisms, monitoring, and optimization. Chemical Reviews, 110, 2795-2838. doi:10.1021/cr900300p
Gross, S., Gilead, A., Scherz, A., et al. (2003) Monitoring photodynamic therapy of solid tumors online by BOLD contrast MRI. Nature Medicine, 9, 1327-1331. doi:10.1038/nm940
Du, L.Y., Umoh, J., Nikolov, H.N., et al. (2007) A quality assurance phantom for the performance evaluation of volumetric micro-CT systems. Physics in Medicine and Biology, 52, 7087-7108. doi:10.1088/0031-9155/52/23/021
Ford, N.L., Graham, K.C., Groom, A.C., et al. (2006) Time-course characterization of the computed tomogram phy contrast enhancement of an iodinated blood-pool contrast agent in mice using a volumetric flat-panel equipped computed tomography scanner. Investigative Radiology, 41, 384-390. doi:10.1097/01.rli.0000197981.66537.48
Graham, K.C., Ford, N.L., MacKenzie, L.T., et al. (2008) Non-invasive quantification of tumour volume in preclinical liver metastasis models using contrast-enhanced x-ray computed tomography. Investigative Radiology, 43, 92-99. doi:10.1097/RLI.0b013e31815603d7
Badea, C.T., Hedlund, L.W., De Lin, M., et al. (2006) Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agents. Contrast Media & Molecular Imaging, 1, 153-164. doi:10.1002/cmmi.103
Aveline, B., Hasan, T. and Redmond, R.W. (1994) Photo physical and photosensitizing properties of benzoporphy rin derivative monoacid ring A (BPD-MA). Photochemistry and Photobiology, 59, 328-335. doi:10.1111/j.1751-1097.1994.tb05042.x
Henderson, B.W. and Dougherty, T.J. (1992) How does photodynamic therapy work? Photochemistry and Photo biology, 55, 145-157. doi:10.1111/j.1751-1097.1992.tb04222.x
Foster, W.K. and Ford, N.L. (2011) Investigating the effect of longitudinal micro-CT imaging on tumour growth in mice. Physics in Medicine and Biology, 56, 315-326. doi:10.1088/0031-9155/56/2/002
Otsu, N. (1979) A threshold selection method from gray level histograms. IEEE Transactions on Systems, Man and Cybernetics, 9, 62-66. doi:10.1109/TSMC.1979.4310076
Busch, T.M., Hahn, S.M., Wileyto, E.P., et al. (2004) Hypoxia and Photofrin uptake in the intraperitoneal car cinomatosis and sarcomatosis of photodynamic therapy patients. Clinical Cancer Research, 10, 4630-4638. doi:10.1158/1078-0432.CCR-04-0359
Phongkitkarun, S., Kobayashi, S., Kan, Z., et al. (2004) Quantification of angiogenesis by functional computed tomography in a matrigel model in rats. Academic Radiology, 11, 573-582. doi:10.1016/S1076-6332(03)00728-1
Shaheen, R.M., Davis, D.W., Liu, W., et al. (1999) Anti angiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Research, 59, 5412-5416.
Hirakawa, S., Fujii, S., Kajiya, K., et al. (2005) Vascular endothelial growth factor promotes sensitivity to ultra violet B-induced cutaneous photodamage. Blood, 105, 2392-2399. doi:10.1182/blood-2004-06-2435
Kan, Z., Phongkitkarun, S., Kobayashi, S., et al. (2005) Functional CT for quantifying tumor perfusion in antian giogenic therapy in a rat model. Radiology, 237, 151-158. doi:10.1148/radiol.2363041293
McGinley, J.N., Knott, K.K. and Thompson, H.J. (2002) Semi-automated method of quantifying vasculature of 1-methyl-1-nitrosourea-induced rat mammary carcinomas using immunohistochemical detection. Journal of Histo chemistry & Cytochemistry, 50, 213-222. doi:10.1177/002215540205000209
Ojha, N., Roy, S., He, G., et al. (2008) Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing. Free Radical Biology and Medicine, 44, 682-691. doi:10.1016/j.freeradbiomed.2007.10.056
Yeh, D.C., Bula, D.V., Miller, J.W., et al. (2004) Expression of leukocyte adhesion molecules in human subfoveal choroidal neovascular membranes treated with and without photodynamic therapy. Investigative Ophthalmology & Visual Science, 45, 2368-2373. doi:10.1167/iovs.03-0981
Kiessling, F., Krix, M., Heilmann, M., et al. (2003) Com paring dynamic parameters of tumor vascularization in nude mice revealed by magnetic resonance imaging and contrast-enhanced intermittent power Doppler sonogram phy. Investigative Radiology, 38, 516-524. doi:10.1097/01.rli.0000073448.16334.fe
Yu, G., Durduran, T., Zhou, C., et al. (2005) Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of thera peutic efficacy. Clinical Cancer Research, 11, 3543-3552. doi:10.1158/1078-0432.CCR-04-2582
Kurohane, K., Tominaga, A., Sato, K., et al. (2001) Pho todynamic therapy targeted to tumor-induced angiogenic vessels. Cancer Letters, 167, 49-56. doi:10.1016/S0304-3835(01)00475-X
Chen, B., Roskams, T., Xu, Y., et al. (2002) Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF-1 mouse tumor model. International Journal of Cancer, 98, 284-290. doi:10.1002/ijc.10175
Van Geel, I.P., Oppelaar, H., Rijken, P.F., et al. (1996) Vascular perfusion and hypoxic areas in RIF-1 tumours after photodynamic therapy. British Journal of Cancer, 73, 288-293. doi:10.1038/bjc.1996.51
Chen, B., Pogue, B.W., Luna, J.M., et al. (2006) Tumor vascular permeabilization by vascular-targeting photo sensitization: Effects, mechanism, and therapeutic implications. Clinical Cancer Research, 12, 917-923. doi:10.1158/1078-0432.CCR-05-1673