Noninvasive Monitoring of Murine Tumor Blood Flow During and After Photodynamic Therapy Provides Early Assessment of Therapeutic Efficacy

• Published in: Clinical cancer research 2005-05, Vol.11 (9), p.3543-3552
• Main Authors: Yu, Guoqiang, Durduran, Turgut, Zhou, Chao, Wang, Hsing-Wen, Putt, Mary E, Saunders, H Mark, Sehgal, Chandra M, Glatstein, Eli, Yodh, Arjun G, Busch, Theresa M
• Format: Article
• Language: English
• Subjects: Animals; blood flow; Blood Flow Velocity - drug effects; broadband diffuse reflectance spectroscopy; diffuse correlation spectroscopy; Dihematoporphyrin Ether - therapeutic use; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Neoplasms, Radiation-Induced - diagnostic imaging; Neoplasms, Radiation-Induced - drug therapy; Neoplasms, Radiation-Induced - physiopathology; Oxygen - metabolism; Photochemotherapy; photodynamic therapy; Prognosis; Sarcoma, Experimental - diagnostic imaging; Sarcoma, Experimental - drug therapy; Sarcoma, Experimental - physiopathology; Spectroscopy, Near-Infrared - methods; tissue hemoglobin oxygen saturation; Treatment Outcome; Ultrasonography, Doppler - methods
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-2582

Purpose: To monitor tumor blood flow noninvasively during photodynamic therapy (PDT) and to correlate flow responses with therapeutic efficacy. Experimental Design: Diffuse correlation spectroscopy (DCS) was used to measure blood flow continuously in radiation-induced fibrosarcoma murine tumors during Photofrin (5 mg/kg)/PDT (75 mW/cm 2 , 135 J/cm 2 ). Relative blood flow (rBF; i.e., normalized to preillumination values) was compared with tumor perfusion as determined by power Doppler ultrasound and was correlated with treatment durability, defined as the time of tumor growth to a volume of 400 mm 3 . Broadband diffuse reflectance spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO 2 ). Results: DCS and power Doppler ultrasound measured similar flow decreases in animals treated with identical protocols. DCS measurement of rBF during PDT revealed a series of PDT-induced peaks and declines dominated by an initial steep increase (average ± SE: 168.1 ± 39.5%) and subsequent decrease (59.2 ± 29.1%). The duration (interval time; range, 2.2-15.6 minutes) and slope (flow reduction rate; range, 4.4 -45.8% minute −1 ) of the decrease correlated significantly ( P = 0.0001 and 0.0002, r 2 = 0.79 and 0.67, respectively) with treatment durability. A positive, significant ( P = 0.016, r 2 = 0.50) association between interval time and time-to-400 mm 3 was also detected in animals with depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after PDT, rBF and SO 2 were predictive ( P ≤ 0.015) of treatment durability. Conclusion: These data suggest a role for DCS in real-time monitoring of PDT vascular response as an indicator of treatment efficacy.