2879 Characterization of Dose Enhancement Produced by Nanoparticles

J. C. Roeske1, L. Nunez2, G. Wiederrecht2, R. R. Weichselbaum1

1University of Chicago, Chicago, IL, 2Argonne National Laboratory, Argonne, IL

Purpose/Objective(s): Recently, there has been significant interest in the use of nanoparticles both for imaging and in cancertherapeutics. In an original study, tumor bearing mice injected with gold nanoparticles and subsequently irradiated had asignificant survival advantage over controls1. It is hypothesized that the increased tumor control is due to the dose enhancementprovided by gold nanoparticles. The goal of this study is to estimate the dose enhancement produced by nanoparticles and todetermine the optimal combination of nanomaterial and ionizing radiation source.

Materials/Methods: A dose enhancement ratio (DER) is defined as 1 � k (�en/�)nano / (�en/�)water where �en/� representsthe spectrum weighted mass-energy absorption coefficient (for water or a particular nanomaterial), and k represents theconcentration of nanoparticles in tissue (k � 0.002)1. The DER represents the factor by which the water equivalent dose inincreased due to the presence of nanoparticles. In order to evaluate the effects of the atomic composition of the nanoparticles,materials with atomic numbers (Z) from 30 to 90 are considered. In addition, the energy spectrum for a number of external beamx-ray sources (50 KVp, 80 KVp, 100 KVp, Co-60 and 6 MV) and radionuclides (I-125, Pd-103, Ir-192 and Cs-137) areevaluated.

Results: The DER is only slightly �1 for Co-60, Ir-192, Cs-137 and 6 MV x-rays across all materials considered. For all ofthese sources, the primary interaction is Compton scattering, and in the energy range of these source emissions, the mass energyabsorption coefficients do not change significantly. However, relatively large increases in the DER are observed for 50 KVp,80 KVp, and 100 KVp x-rays as well as Pd-103 and I-125. For sources with these energies, photoelectric effect dominatesresulting in higher mass energy absorption coefficients as the atomic number increases. As demonstrated in the table, the DERincreases for all sources as Z varies from 30–40. From Z�40–60, the DER plateaus or slightly decreases. For higher Zmaterials (Z�60), the DER increases and is a maximum for the highest Z materials. The highest DER occurs for Z � 90, andranges from 1.25–1.32. That is, nanoparticles would enhance the delivered dose by 25–32%. Higher dose enhancements arepossible with increased nanoparticle uptake by the tumor.

Conclusions: High atomic number nanoparticles coupled with low energy external beam x-rays or brachytherapy sources offerthe potential of enhancing the delivered dose. When combined with a suitable carrier, high Z nanoparticles may result in thedelivery of higher than conventional doses to tumor.

1. Hainfeld JF, et al. Phys Med Biol 49(18):N309–15, 2004.

Author Disclosure: J.C. Roeske, None; L. Nunez, None; G. Wiederrecht, None; R.R. Weichselbaum, None.

2880 A Hybrid MicroCT Scanner for Image-Guided Conformal Radiotherapy of Small Animals

E. E. Graves1, R. Chatterjee1, S. S. Gambhir1, C. H. Contag1, A. L. Boyer2

1Stanford University, Stanford, CA, 2Scott & White Hospital, Temple, TX

Purpose/Objective(s): Treatment of small animals with radiation has largely been limited to planar fields shaped using leadblocks, rendering precise localization of radiation as well as treatment of deep-seated tumors impossible. In order to generatemore accurate models of clinical radiation therapy in experimental studies and to develop more effective means of radiosen-sitizing tumors, methods for conformal radiation therapy must be developed. Accurate delivery of X-ray energy to animals willoffer new opportunities for assessing tumor response to radiation and development of new approaches using radiation-induciblegenes.

Materials/Methods: In collaboration with GE Medical Systems (Milwaukee, WI), we have engineered a prototype conformalradiotherapy system based on a commercially available eXplore RS150 microCT scanner. A variable aperture collimatorapparatus, consisting of two planar arrays of six trapezoidal 1 cm thick brass blocks mounted on a rigid frame, has beenconstructed and fixed to the scanner gantry, as shown in Figure 1. Power and serial communication lines to the collimatorassembly are provided by interfaces on the scanner gantry. Using this apparatus, a hybrid imaging/radiotherapy protocol wasdeveloped in which a subject is first imaged with a low-dose, 90 �m resolution CT examination. The radiation target is thenidentified, and the collimator is adjusted to the proper aperture size to encompass the target while the subject is shifted so thatthe target lies at the gantry isocenter. A series of beams spaced over 360° are then delivered to irradiate the target to the desireddose. Dose profiles achievable with this system were evaluated through simulations and phantom measurements.

Results: A dose rate of 2 Gy/minute at isocenter of a water phantom was measured using 120 kVp, 50 mA X-rays, permittingthe delivery of therapeutic doses of radiation in reasonable exposure times. The collimator apparatus can be smoothly adjustedby serial interface-driven rotational motors, producing apertures ranging from 5.5 cm (fully open, allowing CT acquisitions) to0.1 cm. The collimator apparatus weighs approximately 32 pounds and is counterbalanced by adding to existing weights on the

Atomic Number (Z) 50 KVp x-rays 80 KVp x-rays 100 KVp x-rays I-125 Pd-103

30 1.11 1.11 1.11 1.12 1.1140 1.14 1.16 1.16 1.16 1.1350 1.15 1.15 1.16 1.09 1.0760 1.13 1.16 1.17 1.13 1.1270 1.20 1.20 1.20 1.20 1.1880 1.24 1.23 1.26 1.27 1.2490 1.31 1.31 1.32 1.32 1.25

S707Proceedings of the 48th Annual ASTRO Meeting

scanner gantry. Both simulations and phantom measurements demonstrated that the system is capable of delivering approxi-mately spherical dose distributions of minimum size �2 mm.

Conclusions: The hybrid instrument described above is to the best of our knowledge the first device for image-guidedconformal radiotherapy of small animals. This unit will facilitate the delivery of clinically-relevant radiation treatment regimensto experimental models of cancer and other diseases.

Author Disclosure: E.E. Graves, None; R. Chatterjee, None; S.S. Gambhir, None; C.H. Contag, None; A.L. Boyer, None.

2881 Role of Ovarian Transposition Based on the Dosimetric Effects of Craniospinal Irradiation (CSI) on theOvaries: A Case Report

J. D. Mitchell, C. Hitchen, M. T. Vlachaki

New York University School of Medicine, New York, NY

Purpose/Objective(s): CSI with photons may result in ovarian dysfunction and infertility due to radiation beam divergence intothe true pelvis. However, reports of dosimetric analyses of the radiation received by the ovaries in such cases are lacking. Theuse of adjuvant chemotherapy may further increase the risk of ovarian failure. Laparoscopic ovarian transposition removes theovaries from direct radiation exposure and, therefore, provides an option to preserve ovarian function. In this study, we reportthe radiation dosimetry of the ovaries before and after transposition in a female patient with medulloblastoma who underwentCSI.

Materials/Methods: A 31 year-old nulliparous woman underwent complete surgical resection for a standard risk medullo-blastoma of the left medial cerebellum and was offered CSI followed by chemotherapy. Computed tomography (CT) simulationwas used for treatment planning and dose-volume histograms were generated. Before transposition, MRI of the pelvisdemonstrated that both ovaries were within the spinal radiation field. Via laparoscopic transposition, the left ovary was placedadjacent to the lower pole of the left kidney while the right ovary was placed at the lower edge of the liver. Surgical clips atthe most cephalad and caudal aspect of the ovaries permitted their localization on CT-simulation. The prescribed dose to thecraniospinal axis was 2340 cGy with a posterior fossa boost of 3060 cGy delivered at 180 cGy per fraction using 6 MV photons.

Results: The mean, median and maximum doses for both ovaries before and after transposition are shown in Table 1. Beforetransposition, the mean and maximum doses to the ovaries corresponded to 42% and 69.4% of the prescribed dose of 2340 cGyfor the left and to 7.1% and 30.9% of the prescribed dose for the right ovary, respectively. Ovarian transposition decreased themean and maximum doses to 2.9% and 3.6% of the prescribed dose for the left and to 3.7% and 4.4% of the prescribed dosefor the right ovary, respectively.

Conclusions: This is the first report of three-dimensional dosimetric analysis of radiation dose delivered to the ovaries fromCSI before and after lateral ovarian transposition. Given the significant reduction in ovarian dose following transposition, werecommend obtaining an MRI of the pelvis for ovarian localization in females who require CSI with photons. Ovariantransposition should also be considered as an option to maintain hormonal ovarian function and fertility in those cases whereovarian irradiation is otherwise unavoidable.

Author Disclosure: J.D. Mitchell, None; C. Hitchen, None; M.T. Vlachaki, None.

Table 1

Mean Total Dose(cGy)

Median Total Dose(cGy)

Maximum Total Dose(cGy)

Left Ovary 983 1053 1624Left Transposed Ovary 68 70 84Right Ovary 166 129 723Right Transposed Ovary 87 87 103

S708 I. J. Radiation Oncology ● Biology ● Physics Volume 66, Number 3, Supplement, 2006