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

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.

In Molecular Pursuit of Bone Metastasis by Fluciclovine PET

“…The article in this issue entitled “PET Tracer 18 F-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models” by Oka et al . 2 expands our insight into the bone metastatic niche and how it interacts with targeted radionuclides. This article provides novel information describing the histological characteristics of bone metastasis and how this relates to the uptake of the radiotracers- fluciclovine, fluorodeoxyglucose (FDG), choline and hydroxymethylene diphosphonate (HMDP), that have not been previously examined in the literature.…”

Diagnostic Performance of 18F-Fluciclovine in Detection of Prostate Cancer Bone Metastases

“…Oka et al investigated the potential of 18 F-fluciclovine to aid visualization of bone metastases by comparing the performance of 14 C-fluciclovine with that of 3 H-FDG, 3 H-choline and 99m Tc-hydroxymethylene diphosphonate (HMDP) using triple-tracer autoradiography in rat models of osteolytic bone metastases (derived from breast cancer) and osteoblastic bone metastases (derived from prostate cancer) (32). Histological verification confirmed that 14 C-fluciclovine accumulated in areas of metastatic invasion in both the osteoclastic and the osteoblastic models.…”

Amino Acid Metabolism as a Target for Breast Cancer Imaging

“…Preclinical studies have demonstrated substantial success of 18 F-fluciclovine in the detection of osseous metastases. 44,45 Physiologic fluciclovine avidity is seen in the liver, pancreas, and skeletal muscle. The physiologic avidity in the liver will likely limit detection of hepatic metastases, a common site of metastatic disease in patients with breast cancer.…”