Preliminary clinical trasnationl study of ¹⁸F-(2S, 4R) 4-fluoroglutamine PET/CT imaging in 17 breast cancer patients

Objectives: his preliminary clinical study evaluated the safety, uptake kinetics and diagnostic potential of a glutamine analog, ¹⁸F-(2S, 4R) 4-fluoroglutamine (¹⁸F-GLN), in breast cancer patients.

Methods: 17 patients (Female; age 36~69y) with biopsy-proven breast cancer were investigated with MRI and PET/CT; among which13 subjects underwent whole-body dynamic ¹⁸F-GLN PET/CT for up to 60 min after injection (295.0±67.2 MBq). Remaining 4 patients underwent static scans at 30±10 min after injection. Each patient also underwent standard ¹⁸F-FDG PET/CT at 60 min after injection for comparison analysis. The kinetics of uptake in tumors and normal breast tissues were evaluated by maximal standardized uptake values (SUV). As the Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index, the correlation among the Ki-67 index, ¹⁸F-GLN, ¹⁸F-FDG uptake was also investigated. Results: ¹⁸F-GLN was well tolerated in all patients without adverse events. Normal breast tissue background was low (the average SUV was 0.88±0.39), a minor uptake in normal breast was observed and reached the plateau at about 30 min after injection. Uptake of ¹⁸F-GLN in breast tumors was rapid and the SUV was highest between 1 and 10 min after injection and then a gradual washout over time (32.7 % reduction in mean tumor uptake at 60 min after injection). A three-compartment model fitted the tracer kinetics well. Axillary lymph node lesions showed rapid uptake followed by a slower washout than in tumors. It was reasonable to conlcude that an early imaging window (between 1~10 min) provided the best visual results. Breast lesions as defined by MRI and biopsy were clearly visualized by ¹⁸F-GLN (SUV=3.80±1.14; range 2.11~6.86) and ¹⁸F-FDG PET (SUV=10.49±10; range 2.7~43.03) (P<0.05). The number of lesions and axillary lymph nodes detected by ¹⁸F-GLN was consistent with ¹⁸F-FDG and all of them were confirmed to be true-positive by following biopsy. The immunohistochemical staining confirmed a negative correlation between the ratio of SUV_GLN to SUV_FDG (SUV_G-F)and Ki67 index (r= -0.61, P < 0.05).

Conclusions: ¹⁸F-GLN appeared safe for use in humans and showed significant uptake in breast cancer lesions and metastatic lymph nodes. An early imaging window seems to provide the best visual results. The ratio of SUV_GLN to SUV_FDG might be considered as a noninvasive Ki-67 index and might add valuable information about tumor aggressiveness and prognosis. Keywords: Positron emission tomography; Breast cancer; Glutamine transport; Ki67 proliferation index