Interstitial Fluorescence Spectroscopy in the Human Prostate During Motexafin Lutetium‐Mediated Photodynamic Therapy

Abstract

The in vivo fluorescence emission from human prostates was measured before and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). A single side-firing optical fiber was used for both the delivery of 465 nm light-emitting diode excitation light and the collection of emitted fluorescence. It was placed interstitially within the prostate via a closed transparent plastic catheter. Fitting of the collected fluorescence emission spectra using the known fluorescence spectrum of 1 mg/kg MLu in an intralipid phantom yields a quantitative measure of the local MLu concentration. We found that an additional correction factor is needed to account for the reduction of the MLu fluorescence intensity measured in vivo due to strong optical absorption in the prostate. We have adopted an empirical correction formula given by exp (µ eff · 0.97 cm), which ranges from approximately 3 to 16, with a mean of 9.3 ± 4.8. Using a computercontrolled step motor to move the probe incrementally along parallel tracks within the prostate we can determine one-dimensional profiles of the MLu concentration. The absolute MLu concentration and the shape of its distribution are confirmed by ex vivo assay and by diffuse absorption measurements, respectively. We find significant heterogeneity in photosensitizer concentration within and among five patients. These variations occur over large enough spatial scales compared with the sampling volume of the fluorescence emission that mapping the distribution in three dimensions is possible.

The role of photodynamic therapy (PDT) physics

“…In addition to its role in diagnosis, spectroscopy is particularly applicable to PDT in determining the local drug and oxygen concentrations. 56 Photodynamic therapy can cause changes in the concentration and oxygenation of blood in tissue both directly, through photochemical oxygen consumption, and indirectly, through effects on the vasculature and general physiological responses. The monitoring of these responses may, therefore, be predictive of treatment outcome.…”

“…Another group in Toronto, Canada has commercialized a four-channel light source with computerized power control in each channel. Our group has developed an integrated system that incorporates PDT dosimetry that include light fluence rate at multiple points, 108 a three-dimensional map of optical properties, 46 drug concentration distribution, 56 and tissue oxygenation. 98 A kernelbased algorithm was developed to calculate light fluence rate distribution in the optically heterogeneous prostate gland, 109 which, coupled with an optimization engine allows optimization of light source powers to achieve a uniform light fluence distribution.…”

Prostate PDT dosimetry

“…To accomplish this in our prostate PDT protocol, we have designed a side-firing optical probe which can be inserted into the same catheters used for absorption measurements [26]. The same probe is used to deliver excitation light and collect fluorescence.…”

“…The probe is positioned by the motorized positioners, and acquires fluorescence spectra every 2mm along the catheter. The fluorescence measured by this probe is corrected for optical properties using an analytical correction algorithm and fit to determine the contributions of MLu and background fluorescence [26]. Fig.…”

“…Other optical spectroscopic methods [23,24] have been developed to characterize tissue absorption and scattering spectra, which in term provide information about tissue oxygenation and drug concentration. Fluorescence techniques [25,26] can be used to quantify drug concentration and can provide valuable dynamic information relating to the photobleaching of the photosensitizer and oxygen consumption.…”