Parametric Images of Antibody Pharmacokinetics Based on Serial Quantitative Whole-Body Imaging and Blood Sampling

Parametric images for patient 1. (A) α: fractional blood volume (−). (B) K′₁: normalized extravasation rate constant (h⁻¹). (C) k₂: rate constant of washout from extravascular to vascular space (h⁻¹). (D) V′_d: extravascular-to-vascular activity ratio at equilibrium, equal to K′₁/k₂, and closely related to volume of distribution (−). Gray scales are to right of each image, with maximum and minimum values displayed. Patient 1 had tumor in abdomen, corresponding to high-contrast region on V′_d image (D).

At top, from left to right, are the parametric images α, K′₁, k₂, and V′_d, showing positions corresponding to time–activity curves for liver (A), heart (B), lung (C), kidney (D), intestinal tract (E), and tumor (F). Decay-corrected activity values from measured images are displayed as crosses. Solid line is fitted total-activity curve (a_i(t)), long dashed line is vascular activity (a_v,i(t)), and short dashed line is extravascular activity (a_ev,i(t)). Correlation coefficient was between 0.97 and 0.99, and no filtering was used for the positions marked.

Distributions of measures of goodness of fit. (A) Filter width applied for successful optimization of patient 1. Black corresponds to no filtering, and white is maximum level applied (19-pixel-wide average filter). (B) Squared correlation coefficient between measured and fitted time–activity curves of patient 1; black implies high correlation. (C) Frequency histogram of filter width required for successful time–activity curve optimization of both patients.

Patient 2. (A and B) Raw-count geometric-mean images acquired at 1.1 and 164 h after injection. (C–F) Parametric images α (C), K′₁ (D), k₂ (E), and V′_d (F), with lower limbs excluded for space reasons. Arrows a–i indicate positions at which parameter values were obtained: a = liver (α = 5 × 10⁻⁵, K′₁ = 1 × 10⁻², V′_d = 1.2), b = heart (α = 6 × 10⁻⁵, K′₁ = 6 × 10⁻³, V′_d = 0.6), c = lung (α = 1 × 10⁻⁵, K′₁ = 4 × 10⁻³, V′_d = 0.3), d = kidney (α = 2 × 10⁻⁵, K′₁ = 3 × 10⁻², V′_d = 1.4), e = intestinal tract (α = 7 × 10⁻⁶, K′₁ = 8 × 10⁻², V′_d = 3), f = paraaortic malignancy (α = 8 × 10⁻⁶, K′₁ = 9 × 10⁻², V′_d = 11), and g, h, and i = iliac, inguinal, and cervical nodes, respectively (α = 1 × 10⁻⁵, K′₁ = 5 × 10⁻², V′_d = 7–10).