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Probing dose enhancement due to clinically-relevant concentration of GNPs and 169Yb gamma-rays using PRESAGE
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J Cho, M Alqathami, F Reynoso, and SH Cho, The University of Texas MD Anderson Cancer Center
BACKGROUND
RESULTS
While notable radiosensitizing effects of GNPs irradiated with kV x-rays have been known for some time, poor depth penetration of kV x-rays partly hampers the clinical translation of GNP-mediated radiosensitization (GMR). Meanwhile, brachytherapy has been proposed as a practical means to implement so-called gold nanoparticle-aided radiation therapy (GNRT) while taking advantage of kV x-rays. Although radionuclides such as 103Pd, 125I and 137Cs (as LDR sources) and 192Ir (as HDR source) are commonly used for brachytherapy, each of them falls short of the characteristics necessary (in terms of their gamma ray spectra) for achieving optimal GMR. On the other hand, the intensity-weighted average energy of 169Yb is just above the K-edge of gold and, according to the published computational studies, GNP-mediated dose enhancement due to 169Yb gamma rays is significantly greater and far reaching compared to other brachytherapy sources. In this investigation, we constructed novel 169Yb seeds with titanium encapsulation and studied its dose enhancing capability with a clinically-relevant concentration of GNPs using volumetric PRESAGE dosimeters.
Three vials each containing a 169Yb brachytherapy source at the bottom was compactly filled with tissue paper to immobilize each source at the bottom of each vial. The vials were then flipped upside down and placed next to each other in a triangular form within a lead container (Fig. 1). For each exposure, a PRESAGE cuvette was placed on top of the three vials (Fig. 2).
Fig. 3:Top - The absorption spectra measured over the visible wavelength region determined the radiochromic response maxima at 633 nm. Bottom - PRESAGE cuvettes exposed to three different dose.
Fig. 4: Top – GNP-PRESAGE and Control cuvettes irradiated with 169Yb seeds of 4 different dose. Bottom - GNP-PRESAGE and Control cuvettes irradiated with 250 kVp x-ray with Er-filter or no Filter.
Fig. 1: Three 169Yb seeds were positioned in the triangle shape in three vials and placed in a lead shield container. The red mark shows the position where PRESAGE cuvettes are located for exposure.
Fig. 2: GNP-PRESAGE cuvette exposed to the dose of 16 Gy at the center of cuvette. The distance between each source and cuvette was approximately 2 mm.
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To experimentally estimate the dose received by each cuvette, both control and GNP-PRESAGE were exposed using 250 kVp orthovoltage x-rays (Philips RT-250) with a 0.35 mm Cu filter, namely “unfiltered beam” and also with a 0.35 mm Cu filter mm Er-filter, namely “Er-filtered beam” using four different doses – 0, 3, 10, and 30 Gy.
The fabrication process of PRESAGE cuvettes were as follows: (i) The radical initiator (tetrabromoethane, 0.56 wt%) and LMG dye (2 wt%) were thoroughly mixed with the diisocyanate Part A (51.2 wt%); (ii) the nanocomposite precursor was made by adding the desired concentration of GNPs to polyol Part B (46.2 wt%) and sonicating for 1 h to ensure complete dispersion of the particles; (iii) the prepared Part B mixture was then added to the Part A, mixed thoroughly; (iv) DBTDL (0.05 wt%) was then added to the mixture with vigorous stirring and then poured into poly(methyl methacrylate) spectrophotometer cuvettes with a wall thickness of 1 mm and internal dimensions of 1 × 1 × 4.5 cm. The cuvettes were then placed in a pressure pot (approx. 60 psi) for 48 h in order to eliminate air bubble entrapment.
The absorption spectra was acquired using a Shimadzu UV-1800 UV-VIS spectrophotometer (Perkin Elmer, Waltham, MA, USA). An absorbance spectrum relates to the change in OD as a function of wavelength and was used to select the optimal wavelength which was 633 nm in all cases (Fig. 3). The net OD change of cuvettes per dose was linear in all cases (Fig. 4). GNP-PRESAGEs exposed to Yb-169 sources showed ~65% increase in ODs compared with controls. When exposed to Er-filtered and unfiltered 250 kVp x-rays, they produced smaller increases in ODs, ~41% and ~37%, respectively. There was a linear relationship between ODs and delivered doses with a goodness-of-fit (R2) greater than 0.99.
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While this observation strongly suggested dose enhancement, it requires a further investigation to properly correlate the observed OD change with the amount of macroscopic or microscopic /local GNP-mediated dose enhancement caused by 169Yb gamma rays.
OBJECTIVES
To probe physical evidence of dose enhancement due to a low/clinically-relevant concentration of gold nanoparticles (GNPs) and Yb-169 gamma rays using PRESAGE dosimeters.
CONCLUSIONS
A notable increase in the ODs (~65%) was observed for GNP-PRESAGEs irradiated by Yb-169 gamma rays. Considering the observed OD increases, it was highly likely that Yb-169 gamma rays were more effective than both Er- filtered and unfiltered 250 kVp x-rays, in terms of producing dose enhancement. Due to several unknown factors (e.g., possible difference in the dose response of GNP-PRESAGEs vs. PRESAGEs), however, further investigations are necessary to establish the feasibility of quantifying the exact amount of macroscopic or microscopic/local GNP-mediated dose enhancement using PRESAGE or similar volumetric dosimeters.
This work was supported by DOD/PCRP grant W81XWH
MATERIALS & METHODS
A PRESAGE cuvette was placed at approximately 2 mm above the plane containing three novel Yb-169 brachytherapy seeds (3.2, 3.2, and 5.3 mCi each) (Fig. 1 & 2). Two types of PRESAGE dosimeters (Fig. 3) were used – plain PRESAGEs (controls) and PRESAGEs impregnated with 0.02 wt. % of GNPs (GNP- PRESAGEs). Each PRESAGE dosimeter was irradiated with different time durations (0 to 24 hours) to deliver 0, 4, 8, 16 and 24 Gy of dose. For a reference/comparison, both types of PRESAGEs were also irradiated using 250 kVp x-rays with/without Er-filter to deliver 0, 3, 10, and 30 Gy of dose. Er- filter was used to emulate 169Yb spectrum using 250 kVp x-rays. The absorption spectra of PRESAGEs were measured using a UV spectrophotometer and used to determine the corresponding optical densities (ODs).
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