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.

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