Yu Evan Y, Duan Fenghai, Muzi Mark, Deng Xuan, Chin Bennett B, Alumkal Joshi J, Taplin Mary-Ellen, Taub Jina M, Herman Ben, Higano Celestia S, Doot Robert K, Hartfeil Donna, Febbo Philip G, Mankoff David A
University of Washington, Seattle, Washington
Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
J Nucl Med. 2015 Mar;56(3):354-60. doi: 10.2967/jnumed.114.146936. Epub 2015 Jan 29.
(18)F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone.
This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent (18)F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in (18)F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between (18)F-fluoride incorporation in tumor and normal bone, (18)F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover.
Eighteen participants enrolled, and 17 underwent interpretable baseline (18)F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential (18)F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in (18)F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47).
This trial provides evidence of the ability (18)F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.
（18）F - 氟化物PET可对骨代谢进行定量成像，并可作为对如达沙替尼（一种有效的SRC激酶抑制剂，对骨有活性）等全身治疗的药效学评估。
这是一项针对多中心转移性去势抵抗性前列腺癌（CRPC）组织生物标志物引导治疗试验（NCT00918385）的成像伴随试验（美国放射学会成像网络[ACRIN]6687）。骨转移性CRPC男性患者在开始使用达沙替尼（每日100毫克）之前和之后12周接受（18）F - 氟化物PET检查。在15厘米视野范围内进行动态成像以进行试验评估。主要终点是确定肿瘤和正常骨中（18）F - 氟化物摄取的变化是否因达沙替尼而发生。其他终点包括达沙替尼在肿瘤和正常骨中（18）F - 氟化物摄取之间的差异效应、骨转移灶中（18）F - 氟化物转运、与无进展生存期（PFS）、前列腺特异性抗原及骨转换标志物的相关性。
18名参与者入组，17名在开始使用达沙替尼之前接受了可解读的基线（18）F - 氟化物PET成像。17名患者中有12名接受了治疗期间的PET成像。通过骨转移灶中SUVmaxavg（动态视野内多达5个肿瘤的最大标准化摄取值[SUVmax]的平均值）确定了对达沙替尼反应的统计学显著变化（P = 0.0002），肿瘤和正常骨之间存在显著的（18）F - 氟化物PET反应差异（P < 0.0001）。骨转移灶中（18）F - 氟化物摄取的变化通过SUVmaxavg与PFS有临界相关性（风险比，0.91；95%置信区间，0.82 - 1.00；P = 0.056）。SUVmaxavg的变化与骨碱性磷酸酶相关（P = 0.0014），但与前列腺特异性抗原无关（P = 0.47）。
本试验提供了证据，证明（18）F - 氟化物PET能够描绘达沙替尼在CRPC骨转移中的治疗反应，与PFS有临界相关性。
