Department of Radiology, Thomas Jefferson University, 1020 Locust Street, JAH 474, Philadelphia PA 19107, USA.
Nucl Med Biol. 2013 Nov;40(8):994-9. doi: 10.1016/j.nucmedbio.2013.08.005. Epub 2013 Sep 24.
Monitoring the effectiveness of therapy early and accurately continues to be challenging. We hypothesize that determination of Human Epidermal Growth Factor Receptor 2 (HER2) mRNA in malignant breast cancer (BC) cells by positron emission tomography (PET) imaging, before and after treatment, would reflect therapeutic efficacy.
WT4340, a peptide nucleic acid (PNA) 12-mer complementary to HER2 mRNA was synthesized together with -CSKC, a cyclic peptide, which facilitated internalization of the PNA via IGFR expressed on BC cells, and DOTA that chelated Cu-64. Mice (n = 8) with BT474 ER+/HER2+ human BC received doxorubicin (DOX, 1.5mg/kg) i.p. once a week for six weeks. Mice (n = 8) without DOX served as controls. All mice were PET imaged with F-18-FDG and 48 h later with Cu-64-WT4340. PET imaging were performed before and 72 h after each treatment. Standardized uptake values (SUVs) were determined and percent change calculated. Animal body weight (BW) and tumor volume (TV) were measured.
SUVs for Cu-64-WT4340 after DOX treatment declined by 54% ± 17% after the second dose, 41% ± 15% after the fourth dose, and 29% ± 7% after the sixth dose, compared with 42% ± 22%, 31% ± 18%, and 13% ± 9% (p<0.05) for F-18-FDG. In untreated mice, the corresponding percent SUVs for Cu-64-WT4340 were 145% ± 82%, 165% ± 39%, and 212% ± 105% of pretreatment SUV, compared with 108% ± 28%, 151% ± 8%, and 152% ± 35.5%, (p<0.08) for F-18-FDG. TV in mice after second dose was 114.15% ± 61.83%, compared with 144.7% ± 64.4% for control mice. BW of DOX-treated mice was 103.4% ± 7.6% of pretreatment, vs. 100.1% ± 4.3% for control mice.
Therapeutic efficacy was apparent sooner by molecular PET imaging than by determination of reduction in TV.
早期准确地监测治疗效果仍然具有挑战性。我们假设，通过正电子发射断层扫描（PET）成像，在治疗前后测定恶性乳腺癌（BC）细胞中的人表皮生长因子受体 2（HER2）mRNA，将反映治疗效果。
WT4340 是一种与 HER2 mRNA 互补的 12 聚体肽核酸（PNA），与促进 BC 细胞中通过 IGF1R 内化的环肽 -CSKC 以及螯合 Cu-64 的 DOTA 一起合成。接受 BT474 ER+/HER2+人乳腺癌的小鼠（n=8）每周腹腔内给予阿霉素（DOX，1.5mg/kg）一次，共六周。未接受 DOX 的小鼠（n=8）作为对照。所有小鼠均接受 F-18-FDG 和 48 小时后接受 Cu-64-WT4340 PET 成像。在每次治疗前后均进行 PET 成像。测定标准化摄取值（SUV）并计算百分比变化。测量动物体重（BW）和肿瘤体积（TV）。
DOX 治疗后，Cu-64-WT4340 的 SUV 在第二次剂量后下降 54%±17%，第四次剂量后下降 41%±15%，第六次剂量后下降 29%±7%，而 F-18-FDG 分别下降 42%±22%、31%±18%和 13%±9%（p<0.05）。在未治疗的小鼠中，Cu-64-WT4340 的相应 SUV 百分比分别为治疗前 SUV 的 145%±82%、165%±39%和 212%±105%，而 F-18-FDG 分别为 108%±28%、151%±8%和 152%±35.5%（p<0.08）。第二次剂量后小鼠的 TV 为 114.15%±61.83%，而对照组小鼠为 144.7%±64.4%。DOX 治疗组小鼠的 BW 为治疗前的 103.4%±7.6%，而对照组小鼠为 100.1%±4.3%。
通过分子 PET 成像比通过 TV 减少确定治疗效果更快。
