PET Tracer F-18-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models

• Type of Material: Article
• Authors: Shuntaro Oka, Nihon Mediphys Co. Ltd; Masaru Kanagawa, Nihon Mediphys Co. Ltd; Yoshihiro Doi, Nihon Mediphys Co. Ltd; David Schuster, Emory University; Mark Goodman, Emory University; Hirokatsu Yoshimura, Nihon Mediphys Co. Ltd
• Language: English
• Date: 2017-01-01
• Publisher: Ivyspring International Publisher
• Publication Version: Final Published Version
• Copyright Statement: © Ivyspring International Publisher.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7150/thno.19883
• Title of Journal or Parent Work: Theranostics
• ISSN: 1838-7640
• Volume: 7
• Issue: 7
• Start Page: 2048
• End Page: 2064
• Keywords: DIAGNOSIS; Research & Experimental Medicine; TRANSPORT MECHANISMS; triple-tracer autoradiography; Life Sciences & Biomedicine; osteolytic/osteoblastic metastasis; PROSTATE-CANCER CELLS; BRAIN-TUMORS; prostate cancer; Science & Technology; FDG-PET; breast cancer; CLINICAL-TRIAL; Medicine, Research & Experimental; ACID; BREAST-CANCER; INFLAMMATION; C-11-CHOLINE PET/CT; fluciclovine
• Research Categories: Health Sciences, Oncology; Chemistry, Pharmaceutical

Abstract

18F-Fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid; anti-18F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice; however, such lesions have not been described histologically. Methods: We investigated the potential of 14C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with 3H-2-deoxy-2-fluoro-D-glucose (3H-FDG), 3H-choline chloride (3H-choline), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) by using triple-tracer autoradiography in rat breast cancer osteolytic (on day 12 ± 1 postinjection of MRMT-1) and prostate cancer osteoblastic (on day 20 ± 3 postinjection of AT6.1) metastatic models. Results: The distribution patterns of 14C-fluciclovine, 3H-FDG, and 3H-choline, but not 99mTc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. 99mTc-HMDP accumulated mostly in osteoblastic lesions. 14C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in 14C-fluciclovine and 3H-FDG existed, based on histological differences: low 14C-fluciclovine and high 3H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with 14C-fluciclovine was not clear, yet clearer than with 3H-FDG. Although half of the osteoblastic lesions with 14C-fluciclovine accumulation showed negligible 3H-choline accumulation in comparison, they were histologically similar to lesions with marked 14C-fluciclovine and 3H-choline accumulation. Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions.