Comparison between Fractionated High Dose Rate Irradiation and Continuous Low Dose Rate Irradiation in Spheroids

Omura, Motoko; Torigoe, Soichiro; Kurihara, Hiroaki; Matsubara, Sho; Kubota, Nobuo

doi:10.1080/028418698430043

Cited by 9 publications

(4 citation statements)

References 18 publications

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“…Thus, therapeutic doses can be applied in radiation times well below 1 h. In contrast, radiation dose in RIT is deposited during several days, with continuously decreasing dose rate. Because higher dose rate is more effective in achieving cell damage [5][6][7], it might be assumed that this difference accounts for the extremely high doses necessary in RIT as compared to conventional radiation, to achieve elimination of the target volume.…”

Section: Introductionmentioning

confidence: 99%

Influence of dose rate on therapeutic success of radioiodine therapy of functional thyroid autonomy

Puille

Klett²,

Steiner³

et al. 2005

Nuclear Medicine Communications

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Section: Introductionmentioning

confidence: 99%

Influence of dose rate on therapeutic success of radioiodine therapy of functional thyroid autonomy

Puille

Klett²,

Steiner³

et al. 2005

Nuclear Medicine Communications

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“…The human squamous lung cancer cell line SQ5 was donated by Dr Kubota of the Ibaraki Prefectural University of Health Sciences. (15) Both cell lines were maintained in αMEM medium (Sigma, St Louis, MO, USA) with l-glutamine supplemented with 10% heatinactivated fetal bovine serum (Equitech-Bio, Kerrville, TX, USA), 50 units/mL penicillin, and 50 µg/mL streptomycin. Cells were maintained in exponential growth in humidified incubators at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

Kang¹,

Omura²,

Suzuki³

et al. 2006

Cancer Science

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The objective of the present study was to establish an orthotopic tumor transplantation model in nude mice that closely resembles the clinical features of human lung cancer. The human lung adenocarcinoma A549 cell line and the squamous cell carcinoma SQ5 cell line were used. Tumor cells suspended in serum-free medium were injected directly into the main bronchi of anesthetized female Balb/c athymic nude mice (7-9 weeks old) with or without simultaneous administration of 0.01 M ethylenediaminetetracetic acid (EDTA). In some experiments, lung carcinoma cells harvested from tumors transplanted subcutaneously were recultured and used for intratracheal implantation. Tumor nodules that formed in the lung were counted and confirmed by histological examination. Administration of A549 cells with EDTA resulted in a 70% engraftment rate (n = 10). Recultured A549 cells without and with EDTA resulted in 20% (n = 5) and 80% (n = 5) engraftment rates, respectively. Administration of SQ5 cells without or with EDTA formed 50% (n = 4) and 67% (n = 6) engraftment rates, respectively. Recultured (1) In Japan, lung cancer caused 12.7% of cancer-related mortalities in women and 22% of cancer-related mortalities in men in 2001. (2) In addition, no more than 14.9% of patients survived after treatment for lung cancer. It is a general consensus that the poor prognosis of patients with lung cancer reflects the aggressive biological nature of the cancer as well as the ineffectiveness of early detection procedures and treatment.Efforts have been made to develop effective treatments for lung cancer using an in vivo model. For example, an orthotopic transplantation model of human small-cell lung carcinoma (SCLC) demonstrates sensitivity to cisplatin and resistance to mitomycin C, reflecting the clinical situation. In contrast, the same tumor xenograft implanted subcutaneously responded to mitomycin C and not to cisplatin, thus failing to match the clinical behavior of SCLC.(3) Organ microenvironment may influence the phenotype and sensitivity to chemotherapeutics of tumor cells, as described originally by Pagets' 'seed and soil' theory (4) and confirmed by others.(5,6) Therefore, it is essential to establish a clinically relevant in vivo model that simulates the clinical features for lung cancer research.Several orthotopic transplantation models of lung cancer have been developed in rodents. Examples include direct implantation of human cancerous tissue (7) and injection of tumor cells into the rodent airway, (8,9) pleural cavity, (10,11) or lung parenchyma after skin incision (12) or thoracotomy. (13,14) However, the complex technique for performing transplantation in these models limited their widespread use. Most of the research and development of novel diagnostics and therapeutics for lung cancer still rely on subcutaneous tumor models, which are potentially less clinically relevant.In the present study, we developed a new orthotopic transplantation human lung cancer model in athymic nude mice using a reproducible technique. The presen...

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“…An intraperitoneal administration of radioactivity would likely yield treatment protocols of several days. As such, a more detailed approach would require the use of a model that incorporates the effects of the cell cycle, including repopulation (Zaider and Minerbo 2000, Howell et al 1998, Dale 1996, Omura et al 1998. Furthermore, the radiation sensitivity of cells within micrometastases would show variability, particularly in spheroids large enough to produce hypoxic centres.…”

Section: Discussionmentioning

confidence: 99%

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

Syme¹,

McQuarrie²,

Middleton³

et al. 2003

Phys. Med. Biol.

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A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate significantly on the tumour surface.

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Comparison between Fractionated High Dose Rate Irradiation and Continuous Low Dose Rate Irradiation in Spheroids

Cited by 9 publications

References 18 publications

Influence of dose rate on therapeutic success of radioiodine therapy of functional thyroid autonomy

Influence of dose rate on therapeutic success of radioiodine therapy of functional thyroid autonomy

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

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