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

¹ Department of Medical Radiation Physics, Clinical Sciences, Lund University Hospital, Lund, Sweden; ² Department of Oncology, Clinical Sciences, Lund University Hospital, Lund, Sweden; and ³ Departments of Psychiatry and Radiology, New York State Psychiatric Institute, Columbia University, New York, New York

View larger version (52K): [in this window] [in a new window]   FIGURE 1.  Image data for patient 1. (A) Attenuation map obtained from CT scanogram image. (B) Geometric mean of anteroposterior raw-count images, showing 3 of total of 6 images, acquired at 1.5, 48, and 163 h after injection. (C) Quantitative images in units of MBq/pixel spatially registered to attenuation map.

View larger version (56K): [in this window] [in a new window]   FIGURE 2.  Parametric images for patient 1. (A) : 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).

View larger version (51K): [in this window] [in a new window]   FIGURE 3.  At top, from left to right, are the parametric images , 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 (ai(t)), long dashed line is vascular activity (av,i(t)), and short dashed line is extravascular activity (aev,i(t)). Correlation coefficient was between 0.97 and 0.99, and no filtering was used for the positions marked.

View larger version (35K): [in this window] [in a new window]   FIGURE 4.  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.

View larger version (64K): [in this window] [in a new window]   FIGURE 5.  Patient 2. (A and B) Raw-count geometric-mean images acquired at 1.1 and 164 h after injection. (C–F) Parametric images (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 ( = 5 x 10–5, K'1 = 1 x 10–2, V'd = 1.2), b = heart ( = 6 x 10–5, K'1 = 6 x 10–3, V'd = 0.6), c = lung ( = 1 x 10–5, K'1 = 4 x 10–3, V'd = 0.3), d = kidney ( = 2 x 10–5, K'1 = 3 x 10–2, V'd = 1.4), e = intestinal tract ( = 7 x 10–6, K'1 = 8 x 10–2, V'd = 3), f = paraaortic malignancy ( = 8 x 10–6, K'1 = 9 x 10–2, V'd = 11), and g, h, and i = iliac, inguinal, and cervical nodes, respectively ( = 1 x 10–5, K'1 = 5 x 10–2, V'd = 7–10).

View larger version (64K): [in this window] [in a new window]   FIGURE 6.  Cumulated activity images in patients 1 (A–C) and 2 (D and E). (A) Total cumulated activity (only patient 1 shown). (B and D) Vascular component Ãv. (C and E) Extravascular component Ãev. Ãev images exhibits high contrast values in positions corresponding to confirmed malignant regions, for patient 1 (C) in abdomen and 2 locations in mediastinum, and for patient 2 (E) at cervical, paraaortic, iliac, and inguinal nodes.