In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine

Abstract

Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07). Patients experienced no adverse effects. Conclusion Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. ^© RSNA, 2018 Online supplemental material is available for this article. Clinical trial registration no. NCT01697930.

Figure 1:

Three-dimensional maximum intensity projection PET image obtained 69 minutes after injection of 273 MBq FGln, spanning from midskull to proximal thighs, shows FGln-avid MYC-positive lymphoma (patient 11, Table 1), including biopsy-proven neck adenopathy (arrow). Typical FGln biodistribution is visualized (Table 2).

Figure 2:

Images in patient with SDHB-mutant metastatic paraganglioma and pheochromocytoma (patient 1). Images on left are FGln PET (top) and companion CT (bottom) images obtained in single axial thoracic plane. Images on right are FDG PET (top) and companion CT (bottom) images obtained in corresponding axial thoracic plane and were obtained 2 weeks after FGln PET. Hypermetabolic osteolytic spinal metastasis, with extraosseous component, is present (arrows). FGln PET image was obtained 36 minutes after injection of 148 MBq FGln; at this early time point, tracer accumulation in normal bone (eg, unaffected portion of vertebra, arrowheads) is scant.

Figure 3a:

Detection of SDHB-mutant metastatic renal cancer (patient 3, Table 1) with FGln PET/CT. Corresponding (a) PET, (b) CT, and (c) fusion PET/CT images in single axial thoracic plane obtained 74 minutes after injection of 233 MBq FGln. Nodal mass of metastatic disease in right pulmonary hilum demonstrates distinct tracer avidity (arrow) compared with blood pool (*).

Figure 3b:

Detection of SDHB-mutant metastatic renal cancer (patient 3, Table 1) with FGln PET/CT. Corresponding (a) PET, (b) CT, and (c) fusion PET/CT images in single axial thoracic plane obtained 74 minutes after injection of 233 MBq FGln. Nodal mass of metastatic disease in right pulmonary hilum demonstrates distinct tracer avidity (arrow) compared with blood pool (*).

Figure 3c:

Detection of SDHB-mutant metastatic renal cancer (patient 3, Table 1) with FGln PET/CT. Corresponding (a) PET, (b) CT, and (c) fusion PET/CT images in single axial thoracic plane obtained 74 minutes after injection of 233 MBq FGln. Nodal mass of metastatic disease in right pulmonary hilum demonstrates distinct tracer avidity (arrow) compared with blood pool (*).