With regard to nuclear medicine imaging, there are modalities to evaluate the increased activity of membrane transporters expressed in tumours, such as glucose, amino acid and nucleoside transporters6,7. histopathological hallmarks TG-02 (SB1317) of glioblastoma multiforme (GBM). Furthermore, in both fluorescence and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies, anti-TF 1849 IgG efficiently accumulated in TF-overexpressing intracranial tumours in mice. Although further investigation is required for a future clinical use of immuno-SPECT with 111In-labelled anti-TF 1849 IgG, the immuno-SPECT may represent a unique imaging modality that can visualize the biological characteristics of gliomas differently from those obtained using the existing imaging modalities and may be useful to evaluate the grade of malignancy and determine sampling locations TG-02 (SB1317) for biopsies in patients with glioma, particularly GBM. Introduction Gliomas are the most common type of malignant tumours originating in the central nervous system1. The treatment plan for gliomas is selected based on histopathological diagnosis. Each definitively diagnosed glioma is classified into four grades of malignancy according to the World Health Organization (WHO) classification, and the prognosis of patients with glioma depends on the grade of malignancy2. Although surgical resection is performed based on the policy of maximum TG-02 (SB1317) safe resection as a first step in the treatment of patients with suspicion of glioma3 and the tumour samples resected surgically are used for histopathological diagnosis, tumour samples are obtained through biopsies in patients with tumours located at surgically inaccessible lesions or without tolerability of surgery under general anaesthesia. However, it has been reported that gliomas demonstrate significant intratumoural heterogeneity4, and the sampling error and small quantity of tumour samples obtained through biopsies can lead to inadequate histopathological diagnoses5. For example, the presence of necrosis typically surrounded by pseudopalisading cells and/or microvascular proliferation is essential for the histopathological diagnosis of glioblastoma multiforme (GBM), classified as the most malignant grade 4 glioma based on the WHO classification, and these histopathological hallmarks distinguish GBM from other gliomas. Therefore, if biopsy specimens do not contain necrosis and microvascular proliferation, then the histopathological examination could lead to a misdiagnosis, resulting in the underestimation of the grade. Indeed, a previous study in which a series of patients who underwent tumour resection following tumour biopsy were reviewed revealed that the discrepancy between histopathological diagnoses based on biopsy and tumour resection was 38%5. In addition to conventional magnetic resonance imaging (MRI), several methods for imaging gliomas have been introduced into clinical practice to improve treatment results and diagnostic accuracy6C9. With regard to nuclear medicine imaging, there are modalities to evaluate the increased activity of membrane transporters expressed in tumours, such as glucose, amino acid and nucleoside transporters6,7. Among the modalities, [11C-methyl]-methionine (11C-MET) positron emission tomography (PET) is one of the most common TG-02 (SB1317) modalities used in gliomas because of the generally low uptake in the normal brain, high uptake in the tumour and convenient synthesis of the tracer with high radiochemical purity8,10. Although 11C-MET PET is used for the medical care of gliomas to evaluate the grade of malignancy8,9, there are certain limitations to the accuracy of the evaluation because of overlap in 11C-MET uptake between each grade8,9,11C14. Additionally, 11C-MET PET is also used to determine the sampling location for biopsies7C9,15,16. However, previous studies comparing 11C-MET uptake at biopsy sites and the histopathological findings of tumour samples obtained using biopsies showed that 11C-MET uptake at sites with necrosis decreased compared with that at sites without necrosis, whereas positive correlations were observed between 11C-MET uptake and cell density and between 11C-MET uptake and cell proliferation17C19. Patients with malignancies, including brain tumour, have a higher Nrp1 risk of venous thromboembolism compared with patients without malignancy20. This phenomenon suggests a systemic abnormality of the blood coagulation system in patients with malignancies. Moreover, in patients with GBM, intravascular thrombosis21 and fibrin deposition22 in surgically resected specimens are microscopically TG-02 (SB1317) identified with high frequency. These histopathological findings indicate a blood coagulation system abnormality in the.