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Pharmacokinetics and Biodistribution of ⁸⁶Y-Trastuzumab for ⁹⁰Y Dosimetry in an Ovarian Carcinoma Model: Correlative MicroPET and MRI

¹ Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York
² Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York
³ Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland

View larger version (111K): [in a new window]   FIGURE 1. Dissected mouse. Arrow indicates location of small tumor nodules on spleen.

View larger version (177K): [in a new window]   FIGURE 2. Longitudinal microPET coronal slice images of 86Y-trastuzumab (A), excess unlabeled trastuzumab (B), 86Y-trastuzumab on nontumor-bearing mice (C), 86Y-HuM195 (D), and free 86Y (E). Numbers in upper left corner of each panel indicate time after injection (in hours). Black arrows indicate mAb accumulation at confirmed tumor sites. White arrows indicate injection site.

View larger version (56K): [in a new window]   FIGURE 3. (A) High-resolution transverse MR image slices, registered to corresponding microPET slices. Contours depicting outer periphery of mouse and also collection of tumor nodules near spleen are shown. (B) Two transverse MR slices, obtained on small-animal (4.7 T) scanner, are shown. Two slices are taken at different transaxial positions. Slice on left is through spleen (yellow contour), kidneys (blue), and tumor nodules (orange). Slice on right is posterior to left slice and depicts multiple small tumor nodules in mesentery.

View larger version (20K): [in a new window]   FIGURE 4. (A) Time–activity curve over injection site. Relative activity concentrations were determined by drawing ROIs on microPET image sets. Data are corrected for acquisition time, physical decay, and background. Error bars represent SE. (B) Time–activity curves for blood (triangles) and tumor (squares). Open symbols represent relative activity concentration (e.g., pharmacokinetics) derived from repeated microPET imaging. Activity concentrations (%IA/g) in dissected tissue (solid symbols) were used to quantitate image-based relative concentrations. Error bars represent combined standard uncertainty. Lines show fits used for cumulated activity calculations.

View larger version (21K): [in a new window]   FIGURE 5. Uptake in various tissues 6 d after intraperitoneal injection with 86Y-trastuzumab (86Y-Herceptin), excess unlabeled (cold) trastuzumab, and 86Y-HuM195. Mean values and SE are shown.