Article Figures & Data
Figures
- FIGURE 1.
Three-compartmental model for AMT kinetics in lung tumor, using first-order rate constants (17). Transport rate constant K1 and outflow rate constant k2 describe exchange of AMT between vascular space (CP) and cell cytoplasm, in which it comprises free compartment (Cf). Irreversible enzymatic conversion of AMT to its metabolites (in metabolic pool, Cm) is characterized by metabolic rate constant k3. Efflux of AMT metabolites from metabolic compartment can be represented by rate constant k4. Although, theoretically, AMT metabolites could move from Cm to both Cf and CP, applied kinetic modeling included efflux of tracer metabolites from entire tissue compartment. Dotted arrow represents k4, which was poorly identifiable in full model and eventually set to zero; thus, final analysis included only 3 kinetic rate constants (K1, k2, and k3).
- FIGURE 2.
(A) Images of AMT tracer uptake between 40 and 60 min after injection (left) in patient with benign cyst (patient 1, Table 2). There is low accumulation of tracer in cyst, with activity being lower than normal lung tissue at all time points. (B) Images of AMT tracer uptake between 40 and 60 min after injection (left) in patient with NSCLC with multiple local metastases (patient 6, Table 2). Images show high accumulation in tumor tissue (2-NSCLC, Table 2) and excellent contrast between tumor and lung tissue. ROIs were defined for tumor nodules (white arrows) and lung tissue (black arrows). Corresponding tumor time–activity curve (right) indicates rapid initial uptake of AMT, followed by slight decrease at late time points. Curve fit applying reduced compartmental model (k4 = 0) is shown as solid line, and full compartmental model is displayed as broken line. In addition, 2-compartmental model fit is shown for lung tissue. (C) Representative image of AMT tracer uptake between 40 and 60 min after injection (left) in patient (patient 10, 2-NSCLC, Table 2). Two tumor sites were identified in this patient on basis of CT and 18F-FDG, which both were believed to represent NSCLC. First tumor (1-NSCLC, Table 2) showed time–activity curves similar to Figure 2B and high 18F-FDG SUV. In contrast, second site (orange arrow) showed relatively low uptake. Inspection of corresponding time–activity curve showed high initial uptake, with subsequent plateau followed by tracer washout. Neither full nor reduced (shown) 3-compartmental model fit data well; however, parameter identifiability was much improved using reduced model (CN 5.3 vs. 21.8).
- FIGURE 3.
Correlation between unidirectional uptake rate (K) derived from reduced compartmental model (k4 = 0) and either k3 parameter (A) or SUV for AMT (B). Tumors obtained from different patients are marked by different symbols. k3 parameter was highly correlated with K, indicating that metabolic conversion is dominant factor in AMT tracer uptake in tumors. Moreover, K was also significantly correlated with SUV for AMT, suggesting that this semiquantitative value can provide estimate of magnitude of metabolic conversion.
- FIGURE 4.
(A) Correlation of K values derived from reduced compartmental fit and Patlak graphical analysis. r was determined as 0.83, indicating an excellent correlation between these 2 measures. Tumors obtained from different patients are marked by different symbols. (B) Excellent correlation was also determined between VD determined using compartmental fit and Patlak graphical analysis.
Tables
Time between 18F-FDG and AMT PET SUV Patient no. Sex Age (y) Diagnosis Previous therapy (before AMT) Lesion no. 18F-FDG AMT 1 F 54 Thymic cyst None 18F-FDG PET not done 1 — 0.5 2 M 39 Hamartoma None 54 d (18F-FDG later) 1 0.9 0.7 3 M 66 Metastasis (rectal cancer) None 11 d 1 2.8 1.3 4 M 58 NSCLC (scc) Chemotherapy (2 wk)* 1 mo 1 15.7 2.5 5 F 58 NSCLC (pd) Radiotherapy + chemotherapy (>6 mo)† 1 mo 1 8.0 5.5 2 6.8 4.4 6 F 56 NSCLC (lcc) Radiotherapy + chemotherapy (>6 mo)† 7 d 1 5.5 2.4 2 2.8 2.7 3 3 2.6 4 2.7 1.6 5 2.7 2.7 7 M 79 NSCLC (acc) None 6 d 1 2.8 1.2 8 M 49 NSCLC (scc) None 11 d 1 7.3 2.1 2 3.3 1.7 9 F 47 NSCLC (acc) None 18F-FDG PET not done 1 — 3.2 2 — 3.0 10 M 46 NSCLC (pd) None 28 d 1 4.7 1.9 2 1.6 0.8 ↵* Therapy started after 18F-FDG PET but 2 wk before AMT PET scan.
↵† Therapy was finished more than 6 mo before AMT PET scan.
scc = squamous cell carcinoma; pd = poorly differentiated carcinoma; lcc = large cell carcinoma; acc = adenocarcinoma.
Tumors are consecutively numbered in patients with multiple lesions.
Patient no. Lesion K1 (mL/g/min) k2 (min−1) k3 (min−1) K (mL/g/min) Patlak slope 1 Thymic cyst 0.012 0.092 0.019 0.0021 0.0017 2 Hamartoma 0.098 0.292 0.006 0.0019 0.0016 3 Metastasis 0.098 0.279 0.006 0.0020 0.0007 4 NSCLC* 0.170 0.179 0.008 0.0070 0.0051 5 1-NSCLC 0.287 0.195 0.017 0.0236 0.0108 2-NSCLC 0.187 0.170 0.022 0.0213 0.0074 6 1-NSCLC 0.073 0.067 0.01 0.0096 0.0088 2-NSCLC 0.128 0.131 0.015 0.0129 0.0107 3-NSCLC 0.104 0.105 0.014 0.0125 0.0095 4-NSCLC 0.064 0.117 0.017 0.0082 0.0043 5-NSCLC 0.063 0.036 0.006 0.0092 0.0035 7 NSCLC† 0.082 0.210 0.008 0.0031 0.0030 8 1-NSCLC 0.176 0.131 0.011 0.0134 0.0074 2-NSCLC* 0.275 0.211 0.004 0.0053 0.0058 9 1-NSCLC 0.242 0.213 0.037 0.0359 0.0180 2-NSCLC 0.184 0.151 0.026 0.0266 0.0152 10 1-NSCLC 0.114 0.070 0.011 0.0145 0.0078 2-NSCLC* 0.151 0.201 0.01 0.0075 0.0034 Total Mean NSCLC 0.153 0.146 0.014 0.0140 0.0081 Total SD 0.073 0.058 0.008 0.0091 0.0043 Mean for unaffected lungs 0.036 0.208 — — — SD for unaffected lungs 0.014 0.047 — — —
