Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.
Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.
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DOI：
10.1088/1361-6560/abd3ef
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发表时间：
2021-01-29
影响因子：
3.5
通讯作者：
Hope TA
中科院分区：
文献类型：
--
作者：
Tranel J;Feng FY;James SS;Hope TA
急性血液毒性是 β 发射体靶向放射性核素治疗 (TRT) 的常见不良反应。 Alpha 发射器由于其射程较短，因此具有向肿瘤提供高线性能量转移 (LET) 辐射的潜力。基于抗体的 TRT 延长了血池半衰期，因此增加了骨髓毒性，这是 α 发射体特别关注的问题。专注于血管和骨骼界面区域的准确 3D 吸收剂量计算可以阐明能量沉积模式。首先，对小梁组织中嵌入中央血管的圆柱形几何模型进行建模。在 GATE 中进行蒙特卡罗模拟时，考虑将 β（177Lu、90Y）和 α 发射体（211At、225Ac）作为仅限于血池的源。随后，将放射源添加到小梁骨室中以模拟骨髓转移浸润（BMMI）。径向分布、剂量体积直方图 (DVH) 和体素相对差异用于评估吸收剂量结果。我们证明，与 β 发射器相比，α 发射器具有更高的局部能量沉积。在圆柱形几何模型中，当源被限制在血池内时，β发射放射性核素对小梁骨的剂量更大，因为α发射器将大部分能量沉积在血管壁的70μm内。在 BMMI 模型中，α 发射器对非目标骨小梁的剂量较低。我们的结果表明，当α发射体被限制在血池中时，如标记为抗体时，由于所传递的吸收剂量的微观分布的差异，血液毒性可能低于预期。
Acute hematologic toxicity is a frequent adverse effect of beta-emitter targeted radionuclide therapies (TRTs). Alpha emitters have the potential of delivering high linear energy transfer (LET) radiation to the tumor attributed to its shorter range. Antibody-based TRTs have increased blood-pool half-lives, and therefore increased marrow toxicity, which is a particular concern with alpha emitters. Accurate 3D absorbed dose calculations focusing on the interface region of blood vessels and bone can elucidate energy deposition patterns. Firstly, a cylindrical geometry model with a central blood vessel embedded in the trabecular tissue was modelled. Monte Carlo simulations in GATE were performed considering beta (177Lu, 90Y) and alpha emitters (211At, 225Ac) as sources restricted to the blood pool. Subsequently, the radioactive sources were added in the trabecular bone compartment in order to model bone marrow metastases infiltration (BMMI). Radial profiles, dose-volume histograms (DVHs) and voxel relative differences were used to evaluate the absorbed dose results. We demonstrated that alpha emitters have a higher localized energy deposition compared to beta emitters. In the cylindrical geometry model, when the sources are confined to the blood pool, the dose to the trabecular bone is greater for beta emitting radionuclides, as alpha emitters deposit the majority of their energy within 70 μm of the vessel wall. In the BMMI model, alpha emitters have a lower dose to untargeted trabecular bone. Our results suggest that when alpha emitters are restricted to the blood pool, as when labelled to antibodies, hematologic toxicities may be lower than expected due to differences in the microdistribution of delivered absorbed dose.
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影响因子：
12.4
作者：
Falzone N;Ackerman NL;Rosales LF;Bernal MA;Liu X;Peeters SG;Soto MS;Corroyer-Dulmont A;Bernaudin M;Grimoin E;Touzani O;Sibson NR;Vallis KA
通讯作者：
Vallis KA
影响因子：
3.5
作者：
Yeom, Yeon Soo;Wang, Zhao Jun;Lee, Choonsik
通讯作者：
Lee, Choonsik
影响因子：
3.5
作者：
Allen, Barry J.;Raja, Chand;Graham, Peter
通讯作者：
Graham, Peter
影响因子：
11.8
作者：
Coleman, RE
通讯作者：
Coleman, RE
DOI：
10.1016/j.nima.2016.06.125
发表时间：
2016-11-01
影响因子：
1.4
作者：
Allison, J.;Amako, K.;Yoshida, H.
通讯作者：
Yoshida, H.