Article Figures & Data
Figures
- FIGURE 1.
Workflow of study. PBMS NLME approach was used to select best fit function based on goodness of fit and Akaike weight. Reference absorbed doses were based on ATP fittings using best-fit function. STP absorbed doses were calculated analogously using only STP data for investigated patient. RDs and RMSEs were used to analyze accuracy of STP absorbed doses against reference absorbed doses. AICc = corrected Akaike information criterion; i = time point; N = total number of patients; NLMEM = PBMS NLME; rAD = reference absorbed dose; rTIA = reference TIA; sAD = STP absorbed dose; sTIA = STP TIA.
- FIGURE 2.
RD values of TIAs obtained from ATP fitting using functions f2, f3, f4a, and f4c to TIAs obtained from ATP fitting using best function according to PBMS NLME method, that is, f6a. Box plots show median, 25th and 75th percentiles, whiskers at 5th and 95th percentiles, and outliers. Percentage RDs for functions f4a or f4c are relatively small because of marginal contribution of uptake phase. Function f3 was added for comparison in Figure 2, as this function is often used in the literature (17,35,39). For broad range of covered sampling times after injection in population investigated here, single biologic elimination phase (as is also case for f2) is insufficient.
- FIGURE 3.
RD values of TIAs obtained using PBMS NLME (NLMEM) function
(Eq. 8), Hänscheid method (Eq. 14), and Madsen method (Eq. 15) for STP dosimetry at time points 1–5. TIAs from ATP fittings calculated using PBMS NLME function f6a were used as reference values. Box plots show median, 25th and 75th percentiles, whiskers at 2.5th and 97.5th percentiles, and outliers. TP = time point. - FIGURE 4.
Time–activity curves from ATP (green lines) and STP (black lines) fittings at time point 3 simulated with function f6a for 4 outlier patients. Estimated individual parameters indicate that these outliers had lowest biologic clearance
(4.8 × 10−3/h to 6.7 × 10−3/h) in population and were relatively lower than fixed effect (9.1 × 10−3/h) (Table 2), a well-known behavior in STP dosimetry (17). P = patient.
Tables
Equation no. Function name K* Maximum percentage CV† Maximum absolute off-diagonal correlation matrix element Akaike weight (%)‡ 1 5 25 0.21 4.5 × 10−62 2 7 —§ —§ — 3 9 41 0.43 1.3 × 10−15 4 9 —§ —§ — 5 9 41 0.43 2.3 × 10−13 6 11 156 0.37 — 7 11 120 0.73 — 8 13 44 0.03 100 9 13 107 0.66 — 10 13 59 0.85 — 11 13 11,836 0.47 — 12 15 54 0.75 — 13 15 2 × 1030 0.59 — ↵* Number of parameters of NLME model for corresponding SOE function.
↵† Maximum percentage CV of fitted parameters for corresponding SOE function (percentage CV was calculated as
(42), with being variance of fixed effect).↵‡ Akaike weight indicates probability with which this function best describes data from analyzed set of functions. Only those SOE functions with percentage CV < 50 and a maximum absolute off-diagonal correlation matrix element < 0.8 were considered.
↵§ Random-effect value
of parameter was not identifiable.Total number of kidney biokinetic data used in this analysis is 315.
- TABLE 2.
Parameters Estimated from ATP Fitting Obtained from Best Function Derived Using PBMS with NLME Modeling (i.e.,
)Model parameters (unit) Fixed effect (percentage CV) Random effect (variance, interpatient variability) (percentage IA)1.64 (29.8) 0.22 (percentage IA)0.84 (27.2) 0.16 (percentage IA)0.49 (43.6) 0.38 * (1/h)6.03 × 10−2 (31.3) 0.30 † (1/h)9.07 × 10−3 (22.6) 0.08 ‡ (1/h)7.19 × 10−2 (42.5) 0.52 Intrapatient variability (a in Supplemental Eq. 3) 0 0.079
Supplemental Data
Files in this Data Supplement:
