Significance: Fluorescence guidance in cancer surgery (FGS) using molecular-targeted contrast agents is accelerating, yet the influence of individual patients’ physiology on the optimal time to perform surgery post-agent-injection is not fully understood. Aim: Develop a mathematical framework and analytical expressions to estimate patient-specific time-to-maximum contrast after imaging agent administration for single- and paired-agent (coadministration of targeted and control agents) protocols. Approach: The framework was validated in mouse subcutaneous xenograft studies for three classes of imaging agents: peptide, antibody mimetic, and antibody. Analytical expressions estimating time-to-maximum-tumor-discrimination potential were evaluated over a range of parameters using the validated framework for human cancer parameters. Results: Correlations were observed between simulations and matched experiments and metrics of tumor discrimination potential (p < 0.05). Based on human cancer physiology, times-to-maximum contrast for peptide and antibody mimetic agents were <200 min, >15 h for antibodies, on average. The analytical estimates of time-to-maximum tumor discrimination performance exhibited errors of <10 % on average, whereas patient-to-patient variance is expected to be greater than 100%. Conclusion: We demonstrated that analytical estimates of time-to-maximum contrast in FGS carried out patient-to-patient can outperform the population average time-to-maximum contrast used currently in clinical trials. Such estimates can be made with preoperative DCE-MRI (or similar) and knowledge of the targeted agent’s binding affinity.

中文翻译：

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预测显像剂给药后的最佳对比时间，为个性化荧光引导手术提供信息


意义：使用分子靶向造影剂的癌症手术（FGS）中的荧光引导正在加速，但个体患者的生理机能对注射药剂后进行手术的最佳时间的影响尚不完全清楚。目的：开发数学框架和分析表达式，以估计单剂和配对剂（靶向剂和对照剂共同给药）方案的显像剂给药后患者特定的最大对比度时间。方法：该框架在小鼠皮​​下异种移植研究中针对三类显像剂（肽、抗体模拟物和抗体）进行了验证。使用经过验证的人类癌症参数框架，在一系列参数上评估了估计最大肿瘤识别潜力时间的分析表达式。结果：观察到模拟和匹配实验以及肿瘤辨别潜力指标之间的相关性 (p < 0.05)。根据人类癌症生理学，肽和抗体模拟剂的最大对比度时间平均为<200 id=21>15小时（对于抗体）。最大肿瘤区分性能时间的分析估计平均误差<10%，而患者之间的方差预计大于100%。结论：我们证明，对患者进行的 FGS 中最大对比度时间的分析估计可以优于目前临床试验中使用的群体平均最大对比度时间。这种估计可以通过术前 DCE-MRI（或类似的）和靶向药物的结合亲和力的知识来进行。