Pharmacokinetic Assessment of ¹⁸F-(2S,4R)-4-Fluoroglutamine in Patients with Cancer

(A) Scatterplot of maximum intratumor K₁-SUV1. K₁ was the kinetic rate constant most closely correlated with SUV1 (measured on last dynamic 5-min frame, 25–30 min after injection). (B) Scatterplot of maximum intratumor k₃-SUV3. (C) Waterfall chart of maximum intratumor K₁ and k₃. (D) Waterfall chart of maximum intratumor SUV1 and SUV3. In both waterfall charts, averages for normal brain tissue are shown as color-coded dashed lines.

Lesions from 2 patients exhibiting different ¹⁸F-FGln pharmacokinetics despite having very similar SUV corrected by body weight (SUV_bw) as measured at 190 min after injection. In both cases, axial view of last dynamic PET frame (5-min acquisition time, 25–30 min after injection) and last imaging frame (∼190 min after injection), fused with corresponding CT, is displayed. Gadolinium-enhanced T1-weighted MRI is included for comparison. Three time–activity curves are shown: for whole lesion; image-derived input function scaled by whole-blood activity concentration as measured from blood samples, patient-specific plasma fraction, and population-based metabolite fraction; and normal brain tissue. Contributions to total PET signal for tumor time–activity curves are shown for first compartment (C₁) and second compartment (C₂). (A) 52-y-old woman with confirmed diagnosis of astrocytoma. ¹⁸F-FGln PET/CT shows 2 cm³ lesion in right frontotemporal region. Mean intratumor K₁, k₂, k₃, k₄, and V_T were 0.28 mL/min/g, 0.08 min⁻¹, 0.002 min⁻¹, 0.001 min⁻¹, and 3.9 mL/cm³, respectively. Corresponding values for normal brain tissue were 0.02 mL/min/g, 0.09 min⁻¹, 0.001 min⁻¹, 0.001 min⁻¹, and 0.5 mL/cm³, respectively. SUV_bw at 30, 90, and 190 min was 4.0, 3.1, and 2.1, respectively. At these 3 time points, signal from second compartment contributed 3%, 14%, and 32% of total PET activity concentration. (B) 70-y-old woman with confirmed diagnosis of non–small cell lung cancer that metastasized to brain. PET image shows metastatic lesion in right parietal region. Mean intratumor K₁, k₂, k₃, k₄, and V_T were 0.13 mL/min/g, 0.13 min⁻¹, 0.09 min⁻¹, 0.02 min⁻¹, and 5.1 mL/cm³, respectively. Corresponding values for normal brain tissue were 0.01 mL/min/g, 0.05 min⁻¹, 0.04 min⁻¹, 0.004 min⁻¹, and 0.7 mL/cm³, respectively. SUV_bw at 30, 90, and 190 min was 1.9, 3.1, and 2.1, respectively. At these 3 time points, signal from second compartment contributed 66%, 82%, and 83%, respectively, of total PET activity concentration.

(A) Scatterplot of baseline vs. follow-up mean intratumor k₃ for 5 patients (8 lesions in total) who underwent 2 ¹⁸F-FGln dynamic PET scans. Every patient is color-coded and annotated according to therapy received between baseline and follow-up PET. Line of identity is shown as dashed line. (B) Corresponding scatterplot of baseline vs. follow-up mean intratumor SUV as measured at 30 min after injection.

A 68-y-old man with confirmed diagnosis of glioblastoma multiforme. (A) Baseline (BL) ¹⁸F-FGln dynamic PET was performed after right parietal occipital craniotomy for resection of heterogeneously enhancing mass centered in right occipital lobe (arrow). Follow-up (FU) ¹⁸F-FGln dynamic PET was performed 13 wk after initiation of treatment with nivolumab and radiotherapy. Gadolinium-enhanced T1-weighted MRI scans were performed 3 and 4 d before BL and FU PET, respectively. When compared with BL MRI scan, enhancing nodule extending toward trigone of right lateral ventricle on FU MRI scan is enlarged and exhibits higher uptake at all imaging time points. (B) Time–activity curves from BL and FU PET for tumor, image-derived input function scaled by whole-blood activity concentration as measured from blood samples, patient-specific plasma fraction and population-based metabolite fraction, and normal brain tissue. Mean intratumor K₁, k₂, k₃, k₄ and V_T as calculated from BL PET was 0.07 mL/min/g, 0.05 min⁻¹, 0.02 min⁻¹, 0.02 min⁻¹, and 2.1 mL/cm³, respectively. Corresponding values as calculated from FU PET were 0.16 mL/min/g, 0.11 min⁻¹, 0.10 min⁻¹, 0.10 min⁻¹, and 2.9 mL/cm³, respectively. (C) Signal from second compartment contributed 23%, 40%, and 47% of total PET activity at 30, 86, and 176 min on BL scan and 50%, 53%, and 53% at 30, 98, and 182 min on FU scan. SUV_bw = SUV corrected by body weight.