BD Technologies & Innovation, 21 Davis Dr., Research Triangle Park, Durham, NC, 27709, USA.
Kinetic Vision, 10651 Aerohub Blvd., Cincinnati, OH, 45215, USA.
Drug Deliv Transl Res. 2023 Sep;13(9):2353-2366. doi: 10.1007/s13346-023-01318-7. Epub 2023 Mar 13.
Subcutaneous (SC) delivery is a preferred route of administration for biotherapeutics but has predominantly been limited to volumes below 3 mL. With higher volume drug formulations emerging, understanding large volume SC (LVSC) depot localization, dispersion, and impact on the SC environment has become more critical. The aim of this exploratory clinical imaging study was to assess the feasibility of magnetic resonance imaging (MRI) to identify and characterize LVSC injections and their effect on SC tissue as a function of delivery site and volume. Healthy adult subjects received incremental injections of normal saline up to 5 mL total volume in the arm and up to 10 mL in the abdomen and thigh. MRI images were acquired after each incremental SC injection. Post-image analysis was performed to correct imaging artifacts, identify depot tissue location, create 3-dimensional (3D) SC depot rendering, and estimate in vivo bolus volumes and SC tissue distention. LVSC saline depots were readily achieved, imaged using MRI, and quantified via subsequent image reconstructions. Imaging artifacts occurred under some conditions, necessitating corrections applied during image analysis. 3D renderings were created for both the depot alone and in relation to the SC tissue boundaries. LVSC depots remained predominantly within the SC tissue and expanded with increasing injection volume. Depot geometry varied across injection sites and localized physiological structure changes were observed to accommodate LVSC injection volumes. MRI is an effective means to clinically visualize LVSC depots and SC architecture allowing assessment of deposition and dispersion of injected formulations.Trial Registration: Not applicable for this exploratory clinical imaging study.
皮下（SC）给药是生物治疗药物的首选给药途径，但主要限于体积低于 3 毫升。随着高体积药物制剂的出现，了解大体积 SC（LVSC）储库的定位、分散以及对 SC 环境的影响变得更加关键。本探索性临床成像研究的目的是评估磁共振成像（MRI）识别和表征 LVSC 注射及其对 SC 组织影响的可行性，其功能取决于给药部位和体积。健康成年受试者在手臂中接受递增生理盐水注射，总量达 5 毫升，在腹部和大腿中接受递增生理盐水注射，总量达 10 毫升。每次 SC 递增注射后采集 MRI 图像。进行图像后分析以校正成像伪影、识别储库组织位置、创建 3 维（3D）SC 储库渲染图，并估计体内团注体积和 SC 组织扩张。LVSC 生理盐水储库可通过 MRI 轻松实现、成像并通过后续图像重建进行定量。在某些情况下会发生成像伪影，需要在图像分析过程中进行校正。为单独的储库以及与 SC 组织边界相关的储库创建了 3D 渲染图。LVSC 储库主要保留在 SC 组织内，并随注射体积的增加而扩张。储库几何形状因注射部位而异，观察到局部生理结构变化以适应 LVSC 注射体积。MRI 是一种有效的临床可视化 LVSC 储库和 SC 结构的方法，可评估注射制剂的沉积和分散。试验注册：对于这项探索性临床成像研究，不适用。
