The poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit. ¹⁸F-fluorthanatrace (¹⁸F-FTT) is an analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response. This study intends to characterize ¹⁸F-FTT pharmacokinetics in breast cancer and optimize image timing for clinical trials. A secondary aim is to determine whether ¹⁸F-FTT uptake in breast cancer correlates with matched frozen surgical specimens as a reference standard for PARP-1 protein. Methods: Thirty prospectively enrolled women with a new diagnosis of breast cancer were injected with ¹⁸F-FTT and imaged dynamically 0–60 min after injection over the chest, with an optional static scan over multiple bed positions starting around 70 min. Kinetic analysis of lesion uptake was performed using blood-pool activity with population radiometabolite corrections. Normal breast and normal muscle reference tissue models were compared with PARP-1 protein expression in 10 patients with available tissue. Plasma radiometabolite concentrations and uptake in tumor and normal muscle were investigated in mouse xenografts. Results: Pharmacokinetics of ¹⁸F-FTT were well fit by Logan plot reference region models of reversible binding. However, fits of 2-tissue compartment models assuming negligible metabolite uptake were unstable. Rapid metabolism of ¹⁸F-FTT was demonstrated in mice, and similar uptake of radiometabolites was found in tumor xenografts and normal muscle. Tumor ¹⁸F-FTT distribution volume ratios relative to normal muscle reference tissue correlated with tissue PARP-1 expression (P < 0.02, n = 10). The tumor–to–normal muscle ratio from a 5-min frame between 50 and 60 min after injection, a potential static scan protocol, closely corresponded to the distribution volume ratio relative to normal muscle and correlated to PARP-1 expression (P < 0.02, n = 10). Conclusion: This study of PARPi analog ¹⁸F-FTT showed that uptake kinetics in vivo corresponded to expression of PARP-1 and that ¹⁸F-FTT quantitation is influenced by radiometabolites that are increasingly present late after injection. Radiometabolites can be controlled by using optimal image acquisition timing or normal muscle reference tissue modeling in dynamic imaging or a tumor–to–normal muscle ratio. Optimal image timing for tumor–to–normal muscle quantification in humans appears to be between 50 and 60 min after injection. Therefore, a clinically practical static imaging protocol commencing 45–55 min after injection may sufficiently balance ¹⁸F-FTT uptake with background clearance and radiometabolite interference for quantitative interpretation of PARP-1 expression in vivo.

聚（二磷酸腺苷-核糖）聚合酶抑制剂 （PARPi） 已在卵巢癌、乳腺癌和前列腺癌中显示出疗效，但目前的生物标志物并不能一致地预测临床益处。¹⁸F-fluorthanatrace （¹⁸F-FTT） 是 rucaparib 的类似物，是一种临床批准的 PARPi，是 PARPi 反应的候选生物标志物。本研究旨在表征乳腺癌中的 ¹⁸种 F-FTT 药代动力学并优化临床试验的图像时序。次要目的是确定乳腺癌中 ¹⁸个 F-FTT 摄取是否与匹配的冷冻手术标本相关，作为 PARP-1 蛋白的参考标准。方法：30 名前瞻性入组的新诊断为乳腺癌的女性注射了 ¹⁸个 F-FTT，并在胸部注射后 0-60 分钟进行动态成像，并在 70 分钟左右开始在多个床位上进行可选的静态扫描。使用血池活性和群体放射性代谢物校正进行病变摄取的动力学分析。将正常乳腺和正常肌肉参考组织模型与 10 例有可用组织的患者的 PARP-1 蛋白表达进行比较。在小鼠异种移植物中研究血浆放射性代谢物浓度和肿瘤和正常肌肉的摄取。结果：¹⁸个 F-FTT 的药代动力学与可逆结合的 Logan 图参考区域模型拟合良好。然而，假设代谢物摄取可以忽略不计的 2 组织隔室模型的拟合是不稳定的。¹⁸个 F-FTT 在小鼠中快速代谢，在肿瘤异种移植物和正常肌肉中发现类似的放射性代谢物摄取。 肿瘤 ¹⁸F-FTT 分布体积比相对于正常肌肉参考组织与组织 PARP-1 表达相关 （P < 0.02， n = 10）。注射后 50 至 60 分钟之间 5 分钟框架的肿瘤与正常肌肉比率，一种潜在的静态扫描方案，与相对于正常肌肉的分布体积比密切相关，并与 PARP-1 表达相关 （P < 0.02，n = 10）。 结论：这项对 PARPi 类似物 ¹⁸F-FTT 的研究表明，体内摄取动力学与 PARP-1 的表达相对应，并且 ¹⁸F-FTT 定量受注射后晚期越来越多地存在的放射性代谢物的影响。放射性代谢物可以通过在动态成像中使用最佳图像采集时间或正常肌肉参考组织建模或肿瘤与正常肌肉比率来控制。人类肿瘤至正常肌肉量化的最佳图像时间似乎在注射后 50 至 60 分钟之间。因此，注射后 45-55 分钟开始的临床实用静态成像方案可以充分平衡 ¹⁸F-FTT 摄取与背景清除和放射性代谢物干扰，以定量解释体内 PARP-1 表达。