Monitoring Tumor Response During Photodynamic Therapy Using Near-infrared Photon-migration Spectroscopy¶

Abstract

Benzoporphyrin-derivative (BPD)-monoacid-ring A photodynamic therapy (PDT) was performed on subcutaneous tumor implants in a rat ovarian cancer model. In order to assess PDT efficacy the tumor and normal tissue optical properties were measured noninvasively prior to and during PDT using frequency-domain photon migration (FDPM). FDPM data were used to quantify tissue absorption and reduced scattering properties (given by the parameters a and s , respectively) at four nearinfrared (NIR) wavelengths (674, 811, 849 and 956 nm). Tissue physiologic properties, including the in vivo concentration of BPD, deoxy-hemoglobin (Hb), oxy-hemoglobin (HbO 2 ), total hemoglobin (TotHb), water (H 2 O) and percent tissue hemoglobin oxygen saturation (%S t O 2 ), were calculated from optical property data. PDT efficacy was also determined from morphometric analysis of tumor necrosis in histologic specimens. All the measured tumor properties changed significantly during PDT. [Hb] increased by 9%, while [HbO 2 ], [TotHb] and %S t O 2 decreased by 18, 7 and 12%, respectively. Using histologic data we show that long-term PDT efficacy is highly correlated to mean BPD concentration in tumor and PDT-induced acute changes in [HbO 2 ], [TotHb] and %S t O 2 (correlation coefficients of 0.829, 0.817 and 0.953, respectively). Overall, our results indicate that NIR FDPM spectroscopy is able to quantify noninvasively and dynamically the PDT-induced physiological effects in vivo that are highly correlated with therapeutic efficacy. tration in tumor during PDT

Monitoring photobleaching and hemodynamic responses to HPPH-mediated photodynamic therapy of head and neck cancer: a case report

“…It is desirable to do concurrent, real-time measurements during PDT and a while after PDT. Previous studies showed that real-time measurements during PDT can provide predictive information [5,18,35,38,41,43,50,51]. It is possible to “filter-out” the treatment light during non-invasive measurements to extract noninvasive parameters during PDT.…”

Local physiological changes during photodynamic therapy

“…In subcutaneous rat tumors the PDT-induced difference in tumor SO 2 was correlated with histological damage (area of necrosis) at 3 days after PDT [24]. Also, luminescence-based monitoring of singlet oxygen production in mouse skin during PDT demonstrates a strong correlation between cumulative singlet oxygen count and response to treatment [27].…”

“…Recently, optical technology has been applied toward the goal of noninvasively monitoring tumor oxygenation in PDTtreated animals [12,[24][25][26]. In studies by Wang et al, diffuse reflectance spectroscopy (DRS) was used to measure tumor hemoglobin oxygen saturation (SO 2 or S t O 2 ) immediately before and after Photofrin-PDT (5 mg/kg, 38 mW/ cm 2 , 135 J/cm 2 ).…”

Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance

“…Indeed, Woodhams, et al [118] reported low fluence rate to lead to a slower rate of decline in the oxygen saturation of liver tissue during the course of light delivery for PDT mediated by aluminum disulphonated phthalocyanine. The power for hemodynamic monitoring to predict PDT-created cytotoxicity or treatment outcome has been demonstrated in rodent studies by several groups [119][120][121][122], including investigations that employed instruments based in DRS or DCS [119,121,122]. More recently, DCS has also been used to identify differences in the consistency of blood flow cycles in murine tumors that may be indicative of the sensitivity of the blood vessels to subsequent stresses such as PDT ( Fig.…”