Murine S factors for liver, spleen, and kidney.
Murine S factors for liver, spleen, and kidney.
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发表时间：
2003-05
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通讯作者：
K. Kolbert;Timotheus Watson;C. Matei;Su Xu;J. Koutcher;G. Sgouros
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作者：
K. Kolbert;Timotheus Watson;C. Matei;Su Xu;J. Koutcher;G. Sgouros
新放射性药物的临床前评价在人体试验开始之前在动物系统中进行。这些研究通常在小鼠或其他啮齿动物模型中进行，对于理解吸收剂量和反应之间的关系非常重要，可以转化为人类的临床前结果。在进行这种计算时，假设电子在局部存款其所有能量，或者使用小鼠解剖结构的理想化模型来确定吸收分数。光子的贡献通常被认为是微不足道的。为了提高这种吸收剂量计算的准确性，已经生成了针对（131）I、（153）Sm、（32）P、（188）Re和（90）Y的小鼠特异性S因子，并将光子和电子部分分别制表。还提供了5个单能电子的吸收分数，能量范围为0.5至2 MeV。方法采用4.7T磁共振成像仪对雌性无胸腺小鼠进行磁共振成像。采集15个T1加权、1.5 mm厚的切片（0.5 mm间隙）。使用先前开发的软件包，三维内部剂量测定（3D-ID），绘制器官轮廓，以获得肝脏，肾脏和脾脏的三维表示。使用点核卷积，根据每个源器官的个体贡献计算每个器官的平均吸收剂量。通过假设放射性在每个器官中均匀分布，获得S因子当量值。通过将不同尺寸球体的3D-ID生成的电子S因子与已发表的数据进行比较，验证了结果。根据基质大小、球体大小和放射性核素，获得1%（256（2）基质）至18%（64（2）基质）的一致性。结果计算了肝、脾、右肾和左肾的S因子值。获得了高达0.33的跨器官电子吸收分数（例如，(90)Y右肾至肝）。S因子值和假设完全吸收电子能量获得的值之间的比较产生了超过190%的差异（（90）Y脾自身剂量）。结论跨器官和自吸收剂量的影响依赖于发射能量和器官几何形状，在小鼠剂量估计中应考虑。用于生成这些S因子的方法适用于其他动物系统，也适用于可通过小动物SPECT或PET成像或通过定量放射自显影获得的不均匀活性分布。
UNLABELLED Preclinical evaluation of new radiopharmaceuticals is performed in animal systems before testing is started in humans. These studies, often performed in murine or other rodent models, are important in understanding the relationship between absorbed dose and response, which can be translated to preclinical results for humans. In performing such calculations, either electrons are assumed to deposit all of their energy locally or idealized models of mouse anatomy are used to determine absorbed fractions. Photon contributions are generally considered negligible. To improve the accuracy of such absorbed dose calculations, mouse-specific S factors for (131)I, (153)Sm, (32)P, (188)Re, and (90)Y have been generated, and the photon and electron portions have been tabulated separately. Absorbed fractions for 5 monoenergetic electrons, ranging in energy from 0.5 to 2 MeV, are also provided. METHODS Female athymic mouse MR images were obtained on a 4.7-T MRI device. Fifteen T1-weighted, 1.5-mm-thick slices (0.5-mm gap) were collected. Using a previously developed software package, 3-dimensional Internal Dosimetry (3D-ID), organ contours were drawn to obtain a 3-dimensional representation of liver, kidneys, and spleen. Using a point-kernel convolution, the mean absorbed dose to each organ from the individual contributions of each source organ were calculated. S factor equivalent values were obtained by assuming a uniform distribution of radioactivity in each organ. Results were validated by comparing 3D-ID generated electron S factors for different-sized spheres with published data. Depending on matrix size, sphere size, and radionuclide, 1% (256(2) matrix) to 18% (64(2) matrix) agreement was obtained. RESULTS S factor values were calculated for liver, spleen, and right and left kidneys. Cross-organ electron-absorbed fractions of up to 0.33 were obtained (e.g., (90)Y right kidney to liver). Comparisons between S factor values and values obtained assuming complete absorption of electron energy yielded differences of more than 190% ((90)Y spleen self-dose). CONCLUSION The effect of cross-organ and self-absorbed dose is dependent on emission energy and organ geometry and should be considered in murine dose estimates. The approach used to generate these S factors is applicable to other animal systems and also to nonuniform activity distributions that may be obtained by small-animal SPECT or PET imaging or by quantitative autoradiography.