Evaluation of LAT1 Expression in Patients With Lung Cancer and Mediastinal Tumors

Author:

Watabe Tadashi,Ose Naoko1,Naka Sadahiro2,Fukui Eriko1,Kimura Toru1,Kanou Takashi1,Funaki Soichiro1,Sasaki Hidetaka3,Kamiya Takashi3,Kurimoto Kenta2,Isohashi Kayako,Tatsumi Mitsuaki,Shimosegawa Eku,Kato Hiroki,Ohgaki Ryuichi4,Kanai Yoshikatsu4,Shintani Yasushi1

Affiliation:

1. Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University

2. Pharmacy

3. Radiology, Osaka University Hospital

4. Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan.

Abstract

Purpose of the Report L-type amino acid transporter-1 (LAT1) is a tumor-specific transporter expressed in various tumor types, with minimal expression in normal organs. We previously demonstrated 18F-fluoro-borono-phenylalanine (18F-FBPA) as a selective PET probe for LAT1 in a preclinical study. Herein, we evaluated LAT1 expression in preoperative patients with lung or mediastinal tumors using 18F-FBPA PET and immunofluorescence staining. Patients and Methods The study population included patients with histopathological diagnosis (n = 55): primary lung cancers (n = 21), lung metastases (n = 6), mediastinal tumors (n = 15), and benign lesion (n = 13). PET scanning was performed 1 hour after the injection of 18F-FBPA (232 ± 32 MBq). Immunofluorescence staining was performed on the resected tumor sections using LAT1 antibody. LAT1 staining was graded on a 4-grade scale and compared with the SUVmax on 18F-FBPA PET. Results A positive correlation was observed between the SUVmax of 18F-FBPA PET and LAT1 expression by immunofluorescence staining (r = 0.611, P < 0.001). The SUVmax of 18F-FBPA was 3.92 ± 1.46 in grade 3, 3.21 ± 1.82 in grade 2, 2.33 ± 0.93 in grade 1, and 1.50 ± 0.39 in grade 0 of LAT1 expression. Although 18F-FBPA PET showed variable uptake in lung cancers and mediastinal tumors, benign lesions showed significantly lower SUVmax than those in malignant lesions (P < 0.01). Conclusions Uptake on 18F-FBPA PET reflected the expression level of LAT1 in lung and mediastinal tumors. It was suggested that 18F-FBPA PET can be used for the precise characterization of the tumor in pretreatment evaluation.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Radiology, Nuclear Medicine and imaging,General Medicine

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