Quantification of biochemical PSA dynamics after radioligand therapy with [177Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model

EJNMMI Physics

Table 2 Model estimates of the final pharmacokinetic model for [¹⁷⁷Lu]Lu-PSMA-I&T

Pharmacokinetic parameters	Estimate (RSE%)	95% CI
Structural parameters
k₁₀ (h⁻¹)	0.253 (5.2%)	0.229–0.281
k₁₂ (h⁻¹)	0.0105 (9.2%)	0.00878–0.0125
Tumor volume on k₁₂^a	0.0910 (30.0%)	0.0350–0.544
k₂₁ (h⁻¹)	0.0629 (6.3%)	0.0555–0.0715
k₁₃ (h⁻¹)	0.0321 (6.9%)	0.0281–0.0368
k₃₁ (h⁻¹)	0.0625 (5.4%)	0.0561–0.0689
k₁₄ (h⁻¹)	0.00967 (9.9%)	0.00807–0.0117
Tumor volume on k₁₄^a	1.08 (7.5%)	0.921–1.24
Cycle 2 on k₁₄^b	0.731 (8.1%)	0.619–0.857
Cycle 3 on k₁₄^b	0.498 (11.3%)	0.407–0.624
Cycle 4–7 on k₁₄^b	0.436 (11.6%)	0.350–0.544
k₄₁ (h⁻¹)	0.0150 (3.4%)	0.0141–0.0161
k₁₅ (h⁻¹)	0.275 (6.8%)	0.240–0.314
k₅₁ (h⁻¹)	0.0247 (6.5%)	0.0216–0.279
B_MAX compartment 2 (MBq)	134 (15.5%)	100–183
V1 (L)	10.3^c
Inter-individual variability
k₁₀ (CV%)	33.1 (18.5%)	27.6–39.7
k₁₃ (CV%)	33.4 (22.2%)	26.8–40.8
k₁₄ (CV%)	63.4 (18.9%)	52.0–75.1
k₁₅ (CV%)	29.1 (35.5%)	20.2–40.0
B_MAX compartment 2 (CV%)	67.0 (36.1%)	49.1–94.2
Inter-occasion variability
k₁₄ (CV%)	37.8 (16.5%)	31.5–44.1
Residual unexplained variability
Proportional error compartment 1 (CV%)	55.5 (29.0%)	39.0–71.6
Additive error compartment 1 (MBq/L)	9.57 (16.8%)	8.02–11.2
Proportional error compartment 2 (CV%)	39.7 (8.6%)	36.7–43.2
Proportional error compartment 3 (CV%)	31.9 (8.5%)	29.4–34.6
Proportional error compartment 4 (CV%)	32.7 (9.7%)	30.0–36.2

95% CI and RSE values were obtained from the SIR
B_MAX maximum binding capacity, CI confidence interval, CV% coefficient of variation, RSE relative standard error, SIR sampling importance resampling, V1 central volume of distribution
^aAdded using a power covariate function: \(P_{cov} = P_{pop} *\left( {\frac{COV}{{COV_{median} }}} \right)^{{\theta_{cov} }}\)
^bAdded as fractional change: \(P_{cov} = P_{pop} * \theta_{cov1}^{cycle 2} * \theta_{cov2}^{cycle 3} *\theta_{cov3}^{cycle 4 - 7}\)
^cFixed parameter