PDF(Pubmed)
Abstract：
UNASSIGNED: Computational models yield valuable insights into biological interactions not fully elucidated by experimental approaches. This study investigates an innovative spatiotemporal model for simulating the controlled release and dispersion of radiopharmaceutical therapy (RPT) using 177Lu-PSMA, a prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical, within solid tumors via a dual-release implantable delivery system. Local delivery of anticancer agents presents a strategic approach to mitigate adverse effects while optimizing therapeutic outcomes.
UNASSIGNED: This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored.
UNASSIGNED: Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (KD) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×107, 7.1×108, and 7.1×109 [Bq]) indicates that an activity of 7.1×108 [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues.
UNASSIGNED: These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing.
UNASSIGNED: This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored.
UNASSIGNED: Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (KD) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×107, 7.1×108, and 7.1×109 [Bq]) indicates that an activity of 7.1×108 [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues.
UNASSIGNED: These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing.
摘要：
■计算模型产生了对实验方法未完全阐明的生物相互作用的有价值的见解。这项研究调查了一种创新的时空模型，用于模拟使用177Lu-PSMA的放射性药物治疗（RPT）的受控释放和分散，前列腺特异性膜抗原（PSMA）靶向放射性药物，通过双重释放可植入递送系统在实体瘤内。抗癌剂的局部递送提出了减轻不良反应同时优化治疗结果的战略方法。
■本研究评估了影响RPT疗效的各种因素，包括缺氧区域延伸，结合亲和力，和初始药物剂量，采用一种新颖的三维计算模型。分析测量了这些因素对肿瘤微环境中放射性药剂浓度的影响。此外，探讨了肿瘤和周围组织内的时空放射性药物分布。
分析表明,与周围正常组织相比,肿瘤区域内的曲线下总浓度面积显著更高。此外，与放射源相比，药物分布表现出明显的优异疗效。此外,延长缺氧区域的低微血管密度增强了药物的可用性，促进改善与PSMA受体的结合并增强治疗效果。解离常数(KD)的降低导致提高的结合亲和力和增加的内化药物浓度。初始放射性（7.1×107、7.1×108和7.1×109[Bq]）的评估表明，7.1×108[Bq]的活性在消除肿瘤细胞和对正常组织的最小影响之间提供了有利的平衡。
■这些发现强调了局部放射性药物输送策略的潜力，并强调了释放的药物相对于放射源（植入物）在有效肿瘤治疗中的关键作用。减少药物与微血管网络的接近度并增强其在肿瘤内的分布促进更有效的治疗结果。该研究为未来的实验研究和临床试验提供了宝贵的见解，旨在完善药物治疗方案，最大限度地减少对体内试验的依赖。
■本研究评估了影响RPT疗效的各种因素，包括缺氧区域延伸，结合亲和力，和初始药物剂量，采用一种新颖的三维计算模型。分析测量了这些因素对肿瘤微环境中放射性药剂浓度的影响。此外，探讨了肿瘤和周围组织内的时空放射性药物分布。
分析表明,与周围正常组织相比,肿瘤区域内的曲线下总浓度面积显著更高。此外，与放射源相比，药物分布表现出明显的优异疗效。此外,延长缺氧区域的低微血管密度增强了药物的可用性，促进改善与PSMA受体的结合并增强治疗效果。解离常数(KD)的降低导致提高的结合亲和力和增加的内化药物浓度。初始放射性（7.1×107、7.1×108和7.1×109[Bq]）的评估表明，7.1×108[Bq]的活性在消除肿瘤细胞和对正常组织的最小影响之间提供了有利的平衡。
■这些发现强调了局部放射性药物输送策略的潜力，并强调了释放的药物相对于放射源（植入物）在有效肿瘤治疗中的关键作用。减少药物与微血管网络的接近度并增强其在肿瘤内的分布促进更有效的治疗结果。该研究为未来的实验研究和临床试验提供了宝贵的见解，旨在完善药物治疗方案，最大限度地减少对体内试验的依赖。
