inviCRO, LLC Boston, 27 Drydock Ave., 7th Floor West, Boston, MA, 02210, USA.
Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Mol Imaging Biol. 2017 Oct;19(5):656-664. doi: 10.1007/s11307-016-1041-y.
Competitive radiolabeled antibody imaging can determine the unlabeled intact antibody dose that fully blocks target binding but may be confounded by heterogeneous tumor penetration. We evaluated the hypothesis that smaller radiolabeled constructs can be used to more accurately evaluate tumor expressed receptors.
The Krogh cylinder distributed model, including bivalent binding and variable intervessel distances, simulated distribution of smaller constructs in the presence of increasing doses of labeled antibody forms.
Smaller constructs <25 kDa accessed binding sites more uniformly at large distances from blood vessels compared with larger constructs and intact antibody. These observations were consistent for different affinity and internalization characteristics of constructs. As predicted, a higher dose of unlabeled intact antibody was required to block binding to these distant receptor sites.
Small radiolabeled constructs provide more accurate information on total receptor expression in tumors and reveal the need for higher antibody doses for target receptor blockade.
竞争性放射性标记抗体成像可以确定完全阻断靶结合的未标记完整抗体剂量，但可能因肿瘤穿透的异质性而受到干扰。我们评估了一个假设，即较小的放射性标记构建物可用于更准确地评估肿瘤表达的受体。
包括二价结合和可变血管间距离的 Krogh 圆柱分布模型，模拟了在增加标记抗体形式剂量的情况下较小构建物的分布。
与较大的构建物和完整抗体相比，<25 kDa 的较小构建物在远离血管的较大距离处更均匀地进入结合位点。这些观察结果与构建物的不同亲和力和内化特性一致。正如所预测的，需要更高剂量的未标记完整抗体来阻断对这些远距离受体位点的结合。
小的放射性标记构建物可提供关于肿瘤中总受体表达的更准确信息，并揭示了需要更高的抗体剂量来阻断靶受体。
