Article Figures & Data
Figures
- FIGURE 1.
Synthesis and characterization of [18F]PFPMD. (A) Synthetic routes of [18F]PFPMD. (B) HPLC coelution profile of [18F]PFPMD and PFPMD. Coinjection of [18F]PFPMD and its corresponding nonradioactive PFPMD HPLC analysis confirmed radioligands. (C) In vitro stability of [18F]PFPMD in saline and in mouse serum at 6 h (n = 3). ACN = acetonitrile; RCP = radiochemical purity; UV = ultraviolet. Kryptofix is a product of Merck.
- FIGURE 2.
In vitro binding study and preclinical imaging study with [18F]PFPMD. (A) Protein-binding results for [18F]PFPMD based on radio–thin-layer chromatography results. (B) Uptake of [18F]PFPMD in 2 NSCLC cell lines at indicated time points (n = 3). (C) Cell uptake and blocking study at 60 min (n = 3). (D) Internalization study in 2 NSCLC cell lines. (E) Representative [18F]PFPMD small-animal PET/CT images at 1 h in tumor-bearing mouse models and before treatment with AMG510 (n = 3). (F) Quantitative analysis of tumor and muscle uptake of [18F]PFPMD in H358/A549 tumor–bearing mice at 1 h after injection (5 for each group). *P < 0.01. ARS-1323 = a KRASG12C inhibitor; GMPPNP = guanosine 5′-[β,γ-imido]triphosphate; GTP = guanosine triphosphate; ns = not statistically significant; WT = wild type.
- FIGURE 3.
Biodistribution of [18F]PFPMD in healthy volunteers. (A) Representative PET images of [18F]PFPMD in healthy man at 5 min, 30 min, 1 h, 2 h, 4 h, and 8 h after injection. (B) Biodistribution of [18F]PFPMD in major organs at 5, 15, 30, 40, 50, 60, 120, 240, and 480 min after injection (n = 5). (C) Radioanalysis of [18F]PFPMD biodistribution in blood samples at 10, 30, 60, 120, 240, and 480 min after injection (n = 3).
- FIGURE 4.
Study design for [18F]PFPMD PET/CT imaging of cancer patients. (A) Schematic diagram of patient enrollment. (B) Summary of finally involved patients for [18F]PFPMD PET/CT scan. ARMS = amplification-refractory mutation.
- FIGURE 5.
[18F]PFPMD PET/CT imaging of NSCLC and CRC patients. (A) Representative [18F]PFPMD PET/CT images of non-KRASG12C and KRASG12C tumors in NSCLC and CRC patients, respectively. (B) SUVmax of [18F]PFPMD and [18F]FDG in non-KRASG12C and KRASG12C tumors, respectively (KRASG12C, n = 6; non-KRASG12C, n = 8). (C) [18F]PFPMD SUVmax of non-KRASG12C tumors, KRASG12C tumors, and healthy tissue in NSCLC patients, CRC patients, and healthy volunteers, respectively (NSCLC: KRASG12C, n = 3; non-KRASG12C, n = 5; healthy, n = 5) (CRC: KRASG12C, n = 3; non-KRASG12C, n = 3; healthy, n = 5). ns = not statistically significant.
Tables
Target organ Estimated absorbed dose (μGy · MBq−1) Mean SD Liver 30.8 11.3 Gallbladder wall 65.3 44.8 Lower large intestine wall 46.5 40.0 Small intestine 38.4 12.0 Upper large intestine wall 11.6 2.4 Stomach wall 5.8 1.1 Pancreas 7.6 1.6 Heart wall 16.5 4.1 Lungs 6.8 1.6 Spleen 15.5 5.4 Kidneys 20.2 2.6 Urinary bladder wall 31.7 14.3 Adrenals 7.1 1.6 Brain 7.9 0.6 Thymus 3.9 0.7 Thyroid 3.2 0.3 Muscle 10.3 2.4 Skin 2.6 0.4 Red marrow 6.6 1.1 Osteogenic cells 5.1 1.1 Breasts 2.2 0.5 Uterus 9.9 2.6 Ovaries 11.1 3.7 Testes 3.5 0.6 Total body 7.7 1.2 Effective dose equivalent (μSv · MBq−1) 18.2 5.5 Effective dose (μSv · MBq−1) 14.3 6.1 - TABLE 2.
General Characteristics of Patients Who Underwent [18F]PFPMD and [18F]FDG PET/CT Imaging
Patient no. Sex Age (y) [18F]PFPMD (MBq) [18F]FDG (MBq) Tumor location Size (cm) Histology KRAS mutation [18F]PFPMD SUVmax [18F]FDG SUVmax Method for KRASG12C detection 1 M 67 286.2 200.5 Left lung (inferior lobe) 6.5 Adenocarcinoma G12C 3.6 8.6 ARMS PCR 2 M 70 247.0 220.5 Left lung (superior lobe) 3.5 Adenocarcinoma G12C 2.9 11.8 ARMS PCR 3 M 67 252.2 259.4 Left lung (inferior lobe) 3.8 Adenocarcinoma G12C 4.2 17.0 ARMS PCR 4 F 56 234.8 235.3 Rectum 6.2 Adenocarcinoma G12C 4.4 16.9 ARMS PCR 5 F 58 244.1 259.8 Sigmoid 9.2 Adenocarcinoma G12C 4.0 24.3 ARMS PCR 6 M 78 211.9 207.0 Rectum 4.2 Adenocarcinoma G12C 3.4 23.6 ARMS PCR 7 M 62 302.5 417.6 Left lung (inferior lobe) 2.6 Adenocarcinoma G12A 2.5 10.8 Gene sequencing 8 M 65 297.8 354.0 Right lung (superior lobe) 1.7 Squamous cell carcinoma G12V 2.3 3.6 Gene sequencing 9 M 75 227.5 251.9 Right lung (superior lobe) 3.1 Squamous cell carcinoma G12V 2.7 4.2 Gene sequencing 10 M 67 235.6 231.6 Hilum of left lung 7.9 Squamous cell carcinoma Non-G12C 2.4 22.7 ARMS PCR 11 M 56 178.8 224.2 Right lung (superior lobe) 6.2 Adenocarcinoma Non-G12C 2.2 15.1 ARMS PCR 12 F 57 258.1 259.2 Sigmoid-rectum 4.0 Adenocarcinoma Non-G12C 2.2 13.8 ARMS PCR 13 M 53 254.8 225.3 Rectum 7.3 Adenocarcinoma Non-G12C 2.5 37.3 ARMS PCR 14 M 65 139.9 194.8 Rectum 3.4 Adenocarcinoma Non-G12C 2.7 19.2 ARMS PCR ARMS = amplification-refractory mutation system.
Non-G12C refers to other KRAS mutation types or no KRAS mutation, as AMRS PCR method detects G12C point only.
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