Abstract
Purpose
A procedure for the measurement of spatial dose rate distribution of beta particles emitted by 186Re-liposomes in tumoral tissue, using HS GafChromic films, is presented.
Methods
HNSCC xenografts were intratumorally injected with 3.7 or 11.1 MBq of 186Re-liposomes, and planar gamma camera images were acquired to determine the liposome retention in the tumor. After imaging, rats were sacrificed and tumors were excised and processed in slices; HS film sections were placed between slices and the tumor lobe was reassembled. Tumors and films were kept in the dark at 4°C for 18 h. After irradiation, films were removed and response was read using a transmission scanner. Films were analyzed to determine two-dimensional spatial dose rate distributions and cumulative dose volume histograms. Dose rate distributions were quantified using a 60Co calibration curve, the 186Re physical half-life, and a perturbation factor that takes into account the effect of the film protective layer.
Results
Dose rate distributions are highly heterogeneous with maximal dose rates about 0.4 Gy h−1 in tumors injected with 3.7 MBq and 1.3 Gy h−1 in tumors injected with 11.1 MBq. Dose volume histograms showed dose distributed in more than 95% and 80% of the tumor when injected with the lower and the higher activity, respectively.
Conclusion
The described procedures and techniques have shown the potential and utility of HS GafChromic film for determination of dose rate distributions in solid tumors injected intratumorally with 186Re-liposomes. The film’s structure and the liposomes’ biodistribution must be taken into account to obtain quantitative dose measurements.
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References
Carlsson J, Aronsson-Forssell E, Hietala S-O, Stigbrand T, Tennvall J. Tumor therapy with radionuclides: assessment of progress and problems. Radiother Oncol 2003;66:107–17.
Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 1999;51:691–743.
Emfietzoglou D, Kostarelos K, Papakostas A, Yang W-H, Ballangrud A, Song H, et al. Liposome-mediated radiotherapeutics within avascular tumor spheroids: comparative dosimetry study for various radionuclides, liposome-systems, and a targeting antibody. J Nucl Med 2005;46:89–97.
Emfietzoglou D, Kostarelos K, Sgouros G. An analytical dosimetry study for the use of radionuclide-liposomes conjugates in internal radiotherapy. J Nucl Med 2001;42:499–504.
Harrington KJ, Mohammadtaghi S, Uster P, Glass D, Peters AM, Vile R, et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Canc Res 2001;7:243–54.
Harrington KJ, Lewasnki CR, Stewart JSW. Liposomes as vehicles for targeted therapy of cancer. Part 1: preclinical development. Clin Oncol 2000;12:2–15.
Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 2005;4:145–60.
Belhaj-Tayeb H, Briane D, Vergote J, Kothan S, Leger G, Bendada SE, et al. In vitro and in vivo study of 99mTc-MIBI encapsulated in PEG-liposomes: a promising radiotracer for tumor imaging. Eur J Nucl Med Mol Imaging 2003;30:502–9.
Medina OP, Zhu Y, Kairemo K. Targeted liposomal drug delivery in cancer. Current Pharm Design 2004;10:2981–9.
Harrington KJ, Rowlinson-Busza G, Syrigos KN, Vile RG, Uster PS, Peters AM, et al. Pegylated Liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in tumor xenograft model. Clin Canc Res 2000;6:4939–49.
Jain RK. Barriers to drug delivery in solid tumors. Sci Am 1994;271:58–65.
Murray JC, Carmichael J. Targeting solid tumors: challenges, disappointments, and opportunities. Adv Drug Deliv Rev 1995;17:117–27.
Bao A, Phillips WT, Goins B, Zheng X, Sabour S, Natarajan M, et al. Potential use of drug carried-liposomes for cancer therapy via direct intratumoral injection. Int J Pharm 2006;316:162–9.
NNDC (National Nuclear Data Center, Brookhaven National Laboratory: http://www.nndc.bnl.gov/chart/), 2006.
Bao A, Goins B, Klipper R, Negrete G, Phillips WT. 186Re-liposome labeling using 186Re-SNS/S complexes: in vitro stability, imaging, and biodistribution in rats. J Nucl Med 2003;44:1992–9.
Niroomand-Rad A, Blackwell CR, Coursey BM, Gall KP, Galvin JM, McLaughlin WL, et al. Radiochromic film dosimetry: Recommendations of AAPM Radiation Therapy Committee Task Group 55. Med Phys 1998;25:2093–115.
ISP (International Speciality Products, Inc.: http://www.ispcorp.com), 2006.
Hirata EY, Cunningham C, Micka JA, Keller H, Kissick MW, DeWerd LA. Low dose fraction behavior of high sensitivity radiochromic film. Med Phys 2005;32:1054–60.
Piermattei A, Fidanzio A, Azario L, Russo A, Perrone F, Capote R, et al. A standard dosimetry procedure for 192Ir sources used for endovascular brachytherapy. Phys Med Biol 2002;47:4205–21.
Sharma SD, Bianchi C, Conte L, Novario R, Bhatt BC. Radiochromic film measurement for anisotropy function for high-dose-rate Ir-192 brachytherapy source. Phys Med Biol 2004;49:4065–72.
Mayer R, Dillenhay LE, Shao Y, Song S, Zhang Y-G, Bartholomew RM, et al. A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media. Int J Radiat Oncol Biol Phys 1993;28:505–13.
Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 1989;24:148–54.
Corbin JL, Miller KF, Pariyadath N, Wherland S, Bruce AE. Preparation and properties of tripodal and linear tetradentate N, S-donor ligands and their complexes containing the MoO22+ core. Inorg Chim Acta 1984;90:41–51.
Alva H, Mercado-Uribe H, Rodriguez-Villafuerte M, Brandan ME. The use of a reflective scanner to study radiochromic film response. Phys Med Biol 2002;47:2925–33.
Flynn AA, Pedley RB, Green AJ, Boxer GM, Boden R, Bhatia J, et al. Antibody and radionuclide characteristics and the enhancement of effectiveness of radioimmunotherapy by selective dose delivery to radiosensitive areas of tumour. Int J Radiat Biol 2002;78:407–15.
Hall EJ. Radiobiology for the radiologist, 4th ed. New York: J.B. Lippincott; 1994.
O’Donoghue M, Bardies M, Wheldon TE. Relationship between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med 1995;36:1902–9.
Bao A, Zhao X, Phillips WT, Woolley FR, Otto RA, Goins B, et al. Theoretical study of the influence of a heterogeneous activity distribution on intratumoral absorbed dose distribution. Med Phys 2005;32:200–8.
Acknowledgements
Luis A. Medina acknowledges the National Institute of Cancerology (Mexico) for hospitality during the development of this study, and the Instituto de Ciencias Nucleares, UNAM, for the calibration of the films. The authors would like to thank Dr. Mohan Natarajan and Xiangpeng Zheng for help with SCC-4 cell culture, Anuradha Soundararajan, Cristina Zavaleta and Maxwell Amurao for help during the image acquisition, and José-Manuel Lárraga for assistance with the Monte Carlo simulations. The authors would also like to thank Dr. Cathy Cutler at the University of Missouri Research Reactor for sponsoring our research under the Reactor Sharing Grant (US Department of Energy grant DE-FG07-02ID14380). This work was also supported in part by DGAPA-UNAM grants IN-108906 and IN-110204.
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Medina, L.A., Goins, B., Rodríguez-Villafuerte, M. et al. Spatial dose distributions in solid tumors from 186Re transported by liposomes using HS radiochromic media. Eur J Nucl Med Mol Imaging 34, 1039–1049 (2007). https://doi.org/10.1007/s00259-006-0297-x
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DOI: https://doi.org/10.1007/s00259-006-0297-x