Tracer search in image-guided surgery of HER2-positive breast cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18058
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Nagasaki University
• Principal Investigator: Otsubo Ryota 長崎大学, 病院(医学系), 講師 (80570043)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: image-guided surgery / 乳癌 / HER2陽性 / 近赤外線 / 蛍光色素

Outline of Final Research Achievements

We hypothesized that a molecularly targeted drug administered preoperatively would produce a masking effect that would inhibit the function of tracers with fluorescent dye attached to trastuzumab (Tmab)/pertuzumab (Pmab), and we conducted experiments in mice. The Tmab + fluorescent dye group after preoperative Tmab administration tended to have lower fluorescence intensity than the control group without preoperative Tmab at all time points from 2-8 days post administration. The same trend was observed when Pmab+Fluorescent Dye was administered after Pmab as preoperative treatment. In addition, intracellular translocation of the HER2 receptor and Tmab/Pmab+ fluorophores was observed in cancer cell lines, and this intracellular translocation circumvented the masking effect described above.

Free Research Field

乳腺外科

Academic Significance and Societal Importance of the Research Achievements

HER2陽性乳癌は乳房部分切除の際に癌が露出する断端陽性となる可能性が高く、術中に癌細胞を可視化するイメージガイド下手術の開発が望まれている。ま た、HER2陽性乳癌の予後は元来不良であるが、TmabやPmabによる分子標的治療薬と化学療法が予後を大きく改善させている。今回実験で証明したマスク効果と細胞内移行はHER2陽性乳癌のイメージガイド下手術の開発の際に重要となってくる、病変の描出不良の原因の一つとなりうる。そのため、マスク効果が生じる前の可視化、つまり手術直前のトレーサー投与、または細胞内移行が完了した後のトレーサー投与が有効である可能性を示唆する結果となった。