High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors.

التفاصيل البيبلوغرافية
العنوان:	High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors.
المؤلفون:	Timmermand OV; Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund 22185, Sweden., Nilsson J; Sahlgrenska Academy, Institute of Clinical Sciences, Department Radiation Physics, University of Gothenburg, Gothenburg 41345, Sweden., Strand SE; Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund 22185, Sweden and Faculty of Medicine, Department of Clinical Sciences Lund, Medical Radiation Physics, Lund University, Lund 22185, Sweden., Elgqvist J; Faculty of Science, Department of Physics, University of Gothenburg, Gothenburg 41296, Sweden.
المصدر:	Medical physics [Med Phys] 2016 Dec; Vol. 43 (12), pp. 6632.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: John Wiley and Sons, Inc Country of Publication: United States NLM ID: 0425746 Publication Model: Print Cited Medium: Internet ISSN: 2473-4209 (Electronic) Linking ISSN: 00942405 NLM ISO Abbreviation: Med Phys Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2017- : Hoboken, NJ : John Wiley and Sons, Inc. Original Publication: Lancaster, Pa., Published for the American Assn. of Physicists in Medicine by the American Institute of Physics.
مواضيع طبية MeSH:	Cell Transformation, Neoplastic* , Signal-To-Noise Ratio, Autoradiography/methods , Prostatic Neoplasms/*pathology, Animals ; Cell Line, Tumor ; Humans ; Male ; Mice ; Prostatic Neoplasms/metabolism ; Radioactivity ; Radiometry ; Tissue Kallikreins/metabolism
مستخلص:	Purpose: The first main aim of this study was to illustrate the absorbed dose rate distribution from ¹⁷⁷ Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of ⁹⁰ Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using ¹⁷⁷ Lu-h11B6, directed against the human kallikrein 2 antigen. Methods: Male immunodeficient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼10 ⁷ LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A″-DTPA after which conjugated h11B6 was mixed with ¹⁷⁷ LuCl 3 . The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purified on a NAP-5 column. About 20 MBq ¹⁷⁷ Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrificed and one tumor was collected from each of the five animals and cryosectioned into 10 μm thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code gate v7.0. Results: The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15 ± 0.15, 0.20 ± 0.18, 0.12 ± 0.17, 0.15 ± 0.16, and 0.23 ± 0.22, for each tumor section, respectively. The absorbed dose rate distribution for ¹⁷⁷ Lu at the time of dissection 10 hpi showed a maximum value of 2.9 ± 0.4 Gy/h (mean ± SD), compared to 6.0 ± 0.9 and 159 ± 25 Gy/h for the hypothetical ⁹⁰ Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for ¹⁷⁷ Lu, ⁹⁰ Y, and alpha-particles, respectively. Conclusions: The initial uptake of ¹⁷⁷ Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical ⁹⁰ Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to ¹⁷⁷ Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.
المشرفين على المادة:	EC 3.4.21.35 (Tissue Kallikreins)
تواريخ الأحداث:	Date Created: 20161203 Date Completed: 20170315 Latest Revision: 20170315
رمز التحديث:	20231215
DOI:	10.1118/1.4967877
PMID:	27908170
قاعدة البيانات:	MEDLINE

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تدمد:	2473-4209
DOI:	10.1118/1.4967877