Grkovski Milan, Fanchon Louise, Pillarsetty Naga Vara Kishore, Russell James, Humm John L
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
EJNMMI Res. 2018 Jun 18;8(1):53. doi: 10.1186/s13550-018-0409-1.
Quantitative imaging can facilitate patient stratification in clinical trials. The hypoxia-activated prodrug evofosfamide recently failed a phase III trial in pancreatic cancer. However, the study did not attempt to select for patients with hypoxic tumors. We tested the ability of F-fluoromisonidazole to predict evofosfamide uptake in an orthotopic xenograft model (BxPC3).
Two forms of evofosfamide were used: (1) labeled on the active moiety (H) and (2) on the hypoxia targeting nitroimidazole group (C). Tumor uptake of evofosfamide and F-fluoromisonidazole was counted ex vivo. Autoradiography of C and F coupled with pimonidazole immunohistochemistry revealed the spatial distributions of prodrug, radiotracer, and hypoxia.
There was significant individual variation in F-fluoromisonidazole uptake, and a significant correlation between normalized F-fluoromisonidazole and both H-labeled and C-labeled evofosfamide. F-fluoromisonidazole and C-evofosfamide both localized in hypoxic regions as identified by pimonidazole.
F-fluoromisonidazole predicts evofosfamide uptake in a preclinical pancreatic tumor model.
定量成像有助于在临床试验中对患者进行分层。缺氧激活前药依沃福酰胺最近在胰腺癌的III期试验中失败。然而，该研究未尝试选择肿瘤缺氧的患者。我们在原位异种移植模型（BxPC3）中测试了F-氟米索硝唑预测依沃福酰胺摄取的能力。
使用了两种形式的依沃福酰胺：（1）标记在活性部分（H）上；（2）标记在缺氧靶向硝基咪唑基团（C）上。依沃福酰胺和F-氟米索硝唑的肿瘤摄取在体外进行计数。C和F的放射自显影结合匹莫硝唑免疫组织化学揭示了前药、放射性示踪剂和缺氧的空间分布。
F-氟米索硝唑摄取存在显著的个体差异，标准化的F-氟米索硝唑与H标记和C标记的依沃福酰胺均存在显著相关性。F-氟米索硝唑和C-依沃福酰胺均定位于匹莫硝唑鉴定的缺氧区域。
F-氟米索硝唑在临床前胰腺肿瘤模型中可预测依沃福酰胺的摄取。
