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

F-Fluciclovine (-1-amino-3-F-fluorocyclobutanecarboxylic acid; -F-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. We investigated the potential of C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with H-2-deoxy-2-fluoro-D-glucose (H-FDG), H-choline chloride (H-choline), and Tc-hydroxymethylene diphosphonate (Tc-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. The distribution patterns of C-fluciclovine, H-FDG, and H-choline, but not Tc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. Tc-HMDP accumulated mostly in osteoblastic lesions. C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in C-fluciclovine and H-FDG existed, based on histological differences: low C-fluciclovine and high H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with C-fluciclovine was not clear, yet clearer than with H-FDG. Although half of the osteoblastic lesions with C-fluciclovine accumulation showed negligible H-choline accumulation in comparison, they were histologically similar to lesions with marked C-fluciclovine and H-choline accumulation. These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions.