Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy.
OBJECTIVE
To monitor tumor blood flow noninvasively during photodynamic therapy (PDT) and to correlate flow responses with therapeutic efficacy.


METHODS
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/cm2, 135 J/cm2). 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 mm3. Broadband diffuse reflectance spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO2).


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, r2= 0.79 and 0.67, respectively) with treatment durability. A positive, significant (P = 0.016, r2= 0.50) association between interval time and time-to-400 mm3 was also detected in animals with depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after PDT, rBF and SO2 were predictive (P < or = 0.015) of treatment durability.


CONCLUSIONS
These data suggest a role for DCS in real-time monitoring of PDT vascular response as an indicator of treatment efficacy.
Yu
Guoqiang
G
Department of Physics and Astronomy, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. guoqiang@physics.upenn.edu
Durduran
Turgut
T
Zhou
Chao
C
Wang
Hsing-Wen
HW
Putt
Mary E
ME
Saunders
H Mark
HM
Sehgal
Chandra M
CM
Glatstein
Eli
E
Yodh
Arjun G
AG
Busch
Theresa M
TM
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy; D011379:Prognosis; D012513:Sarcoma, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler / Q000379:methods
D017323:Dihematoporphyrin Ether; D010100:Oxygen