Prediction and evaluation of therapeutic effect of melphalan, a first-line drug for multiple myeloma: Development of PET imaging method

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09954
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Osaka Medical College (2018); Osaka University (2015-2017)
• Principal Investigator: Isohashi Kayako 大阪医科大学, 医学部, 助教 (50598604)
• Co-Investigator(Kenkyū-buntansha): 畑澤 順 大阪大学, 医学系研究科, 教授 (70198745)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: PET-CT / 多発性骨髄腫 / MET / FDG / FBPA

Outline of Final Research Achievements

Melphalan, a therapeutic agent for multiple myeloma (MM), acts via the tumor cell membrane neutral amino acid transporter (LAT1). If LAT1 expression could be predicted, it would be possible to predict the therapeutic effect. Cell-transplanted small animal tumor models of MM and malignant lymphoma (ML) were created. PET was performed using methionine (MET) and FBPA with high LAT1 affinity and compared to FDG PET. High expression of LAT1 in MM and ML cells was confirmed by flow cytometry. The MM model showed no difference in the uptake of MET, FDG and FBPA, and the ML model showed weak MET, but no difference in the uptake of FDG and FBPA. High LAT1 expression was thought to be related to the uptake of FBPA.

Free Research Field

PET-CT、核医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、多発性骨髄腫（MM）並びに悪性リンパ腫（ML）の腫瘍細胞移植小動物モデルを用いたPET-CT評価を行い、腫瘍細胞のLAT1高発現はアミノ酸トレーサの一つであるFBPAの取り込みと関係があることが示唆された。健常成人におけるmethionine(MET)の生理的集積は肝臓や膵臓で強く、FDGの生理的集積は脳や尿路排泄経路で強い。それに対して、FBPAの生理的集積は尿路排泄経路を除いて各臓器で全体に低く、臨床応用が期待できると考えられた。今後、臨床研究が開始できるように倫理委員会への書類準備並びに申請、薬剤合成の準備などをすすめていく。