Optical properties of human prostate at 732 nm measured in mediated photodynamic therapy

Abstract

Characterization of the tissue light penetration in prostate photodynamic therapy (PDT) is important to plan the arrangement and weighting of light sources so that sufficient light fluence is delivered to the treatment volume. The optical properties (absorption [mu(a)], transport scattering [mu(s)'] and effective attenuation [mu(eff)] coefficients) of 13 patients with locally recurrent prostate cancer were measured in situ using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu)-mediated PDT in four quadrants. Optical properties were derived by applying the diffusion theory to the fluence rates measured at several distances (0.5-5 cm) from a point source. mu(a) and mu(s)' varied between 0.07 and 1.62 cm(-1) (mean 0.37 +/- 0.24 cm(-1)) and 1.1 and 44 cm(-1) (mean 14 +/- 11 cm(-1)), respectively. mu(a) was proportional to the concentration of MLu measured by an ex vivo fluorescence assay. We have observed, on average, a reduction of the MLu concentration after PDT, presumably due to the PDT consumption of MLu. mu(eff) varied between 0.91 and 6.7 cm(-1) (mean 2.9 +/- 0.7 cm(-1)), corresponding to an optical penetration depth (delta = 1/micro(eff)) of 0.1-1.1 cm (mean 0.4 +/- 0.1 cm). The mean penetration depth at 732 nm in human prostate is at least two times smaller than that found in normal canine prostates, which can be explained by a four times increase of the mean value of mu(s)' in human prostates. The mean light fluence rate per unit source strength at 0.5 cm from a point source was 1.5 +/- 1.1 cm(-2), excluding situations when bleeding occurs. The total number of measurements was N = 121 for all mean quantities listed above. This study showed significant inter- and intraprostatic differences in the optical properties, suggesting that a real-time dosimetry measurement and feedback system for monitoring light fluences during treatment should be considered for future PDT studies.

Figure 1

(a) Transrectal ultrasound image of a human prostate, showing the position of source (closed circle) and detector (x) fibers. The source positions labeled 1, 2, 3 and 4 were used for optical properties measurement for the RUQ, LUQ, RLQ and LLQ, respectively, with the detector placed in a separate catheter in each quadrant. The open circle on the right upper quadrant is for a linear source that passed through the position but is too short to have active light component in the cross-section plane. The grid on the template (“+”) is 0.5 cm apart. (b) Schematic of the measurement geometry, illustrating the coordinates used to determine the source–detector distance.

Figure 2

Measurement of light fluence rate (mW/cm²) at different distances, x, from a point source in liquid optical phantoms: (a) ${\mu }_{\mathrm{s}}^{\prime }$ = 3.6 cm⁻¹ and μ_a = 0.02, 0.1 and 0.5 cm⁻¹ and (b) ${\mu }_{\mathrm{s}}^{\prime }$ = 7.2 cm⁻¹, μ_a = 0.02, 0.08 and 0.40 cm⁻¹. Symbols represent measurements with an isotropic detector. The solid lines are the best fit with the resulting fit optical properties (from top to bottom): (a) ${\mu }_{\mathrm{s}}^{\prime }$ = 3.7, 3.8 and 3.4 cm⁻¹ and μ_a = 0.03, 0.097 and 0.53 cm⁻¹ and (b) ${\mu }_{\mathrm{s}}^{\prime }$ = 7.5, 7.1 and 7.3 cm⁻¹, μ_a = 0.022, 0.074 and 0.38 cm⁻¹, respectively.

Figure 3

Measured light fluence rate per unit source strength (ϕ/S) at distances along the catheter, x, from the point source measured in vivo in human prostate gland for Patient 13. Lines are measured data and symbols are fits. (There are too many measured points to express the measured data clearly as symbols.) (a) Light fluence rates in the right lower quadrant (○), right upper quadrant (x) and left upper quadrant (*) of the same prostate before PDT. (b) Light fluence rates before (○) and after (+) light treatment in the right lower quadrant of the prostate gland. The optical properties are ○—μ_a = 0.23 cm⁻¹, ${\mu }_{\mathrm{s}}^{\prime }$ = 7.3 cm⁻¹, ϕ(0.5)/S = 1.1 cm⁻² and h = 0.5; x— μ_a = 0.44 cm⁻¹, ${\mu }_{\mathrm{s}}^{\prime }$ = 12.0 cm⁻¹, ϕ(0.5)/S = 0.78 cm⁻² and h = 0.7; *—μ_a = 0.25 cm⁻¹, ${\mu }_{\mathrm{s}}^{\prime }$ = 11.6 cm⁻¹, ϕ(0.5)/S = 1.3 cm⁻² and h = 0.7; +—μ_a = 0.25 cm⁻¹, ${\mu }_{\mathrm{s}}^{\prime }$ = 6.6 cm⁻¹, ϕ(0.5)/S = 1.0 cm⁻² and h = 0.5 cm.

Figure 4

Light fluence rate vs time measured by the in vivo dosimetry system for the four quadrants for Patient 7 at 732 nm wavelength. Large disturbances of light fluence rate were caused by movement of detector positions, per observation by the operators.

Figure 5

Variation of (a) μ_a, (b) ${\mu }_{\mathrm{s}}^{\prime }$, (c) μ_eff and (d) δ in patients before (open bars) and after (solid bars) PDT. The height of each bar is the mean value measured in each patient. The error bars specify the standard deviation among the four quadrants of a prostate. The solid horizontal line is the average of all measurements, and the dashed lines are the standard deviation of the average.

Figure 6

Measured mean fluence rate per power, ϕ/S, at 0.5 cm from the point source at 732 nm in different patients before (open bars) and after (solid bars) PDT. The error bars reflect intraprostate variation of ϕ/S. The solid horizontal line is the average of all measurements, and the dashed lines are the standard deviation of average: 1.5 ± 1.1 cm⁻².

Figure 7

(a) In vivo absorption coefficient (μ_a) at 732 nm as a function of measured ex vivo MLu concentration (in ng/mg) from the same human prostate. The symbols are measured points in vivo: ○—before PDT, *—after PDT. The solid line is a linear fit to the measured in vivo data. The symbol “+” represents the measured μ_a of MLu vs MLu concentration in a pure liposyn phantom. The dashed line is a linear fit to the phantom data with ${\mu }_{\mathrm{s}}^{\prime }$ = 4 cm⁻¹, (b) Extrapolated MLu concentration from ex vivo fluorescence (bars) and from μ_a (symbols) as a function of injected MLu concentration: open bars (○)—before PDT, solid bar (□)—after PDT. Drug concentration calculated from μ_a uses the linear relationship determined in (a): c (ng/mg) = (μ_a (cm⁻¹) – 0.227)/0.0658. The thin and thick error bars correspond to the standard deviation of the ex vivo biopsy and in vivo absorption measurements, respectively. Notice that (b) used all measured μ_a data (121 points), whereas (a) used a subset of μ_a data (24 points) that had corresponding ex vivo biopsies. (Insufficient data existed to extrapolate tissue concentration from in vivo absorption measurement for 1 mg/kg MLu injection at 6 h drug-treatment time interval before PDT due to bleeding.)