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Radioimmunotherapy of Non-Hodgkin’s Lymphoma with ⁹⁰Y-DOTA Humanized Anti-CD22 IgG (⁹⁰Y-Epratuzumab): Do Tumor Targeting and Dosimetry Predict Therapeutic Response?

¹ Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey
² Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
³ Roswell Park Cancer Center, Buffalo, New York
⁴ University Hospital, René Gauducheau Cancer Center, Nantes, France
⁵ Fox Chase Cancer Center, Philadelphia, Pennsylvania
⁶ University of Oklahoma Health Sciences Center, Department of Radiological Sciences, Oklahoma City, Oklahoma

View larger version (70K): [in a new window]   FIGURE 1. Anterior fast (30 cm/min) whole-body images illustrate distribution of 111In-epratuzumab (0.218 GBq) in 54-y-old man with follicular NHL. Images taken at prevoiding (i.e., 1 h after end of infusion), 4, 24, and 48 h demonstrate blood-pool activity in heart and large blood vessels. Liver and spleen are seen, and bladder is seen only on prevoiding image. Images at 120, 144, and 168 h after injection show heart blood pool fading with persistent liver and spleen activity. There is perineal activity on all images, and nasopharyngeal activity through 48 h, in this patient. Tumor uptake can be seen in left neck and right iliac regions at 24 h. Additional sites in left supraclavicular region, left axilla, and 1 more right iliac/inguinal site are seen at 48 h. Tumor-to-background ratio improves on later images.

View larger version (117K): [in a new window]   FIGURE 2. Posterior image was taken 144 h after injection of 0.215 GBq 111In-epratuzumab in 44-y-old woman who had 3 sites (arrows) of metastatic NHL in right lobe of liver. Uptake was clearly identified with 111In-epratuzumab.

View larger version (28K): [in a new window]   FIGURE 3. Relationship between total radiation-absorbed dose to red marrow dose (cGy) or blood clearance, as represented by effective residence time (RT-E; h/L) and hematologic toxicity (graded at its nadir by National Cancer Institute Common Toxicity Criteria version 2.0). Red marrow dose was determined in most patients by scintigraphic methods. , Group 1; , group 2.

View larger version (18K): [in a new window]   FIGURE 4. Influence of tumor size and targeting on response to 90Y-epratuzumab. Fifteen patients were selected to have measurements of lesions in their baseline and follow-up CT studies. PD was determined from product of LD and a diameter perpendicular to LD through next largest size of lesion. Maximum percentage decrease was determined from follow-up CT studies performed at 1, 3, or 6 mo after 90Y-epratuzumab treatment. Each lesion was also scored against whether it was seen with 111In-epratuzmab using baseline CT as standard comparator. , TP; , FN.

View larger version (27K): [in a new window]   FIGURE 5. Relationships between tumor dosimetry, tumor size, and response. Tumor size was determined from baseline CT. Maximum percentage change in tumor size is based on comparison of baseline measurements of product of 2 longest diameters (PD) compared with follow-up measurements of same lesions at time of their maximum reduction in size. Tumors that progressed in size after treatment were designated as +10%.

View larger version (94K): [in a new window]   FIGURE 6. Patient 1-5 is 46-y-old man with follicular NHL who was treated with 0.829 GBq (22.4 mCi) 90Y-epratuzumab (0.37 GBq/m2, 10 mCi/m2). (A) 111In-Epratuzumab anterior planar image of abdomen at 48 h where heterogeneous tumor uptake in coalescing nodular masses is seen that corresponded with large mesenteric and retroperitoneal masses seen on baseline CT (B). (C) Sixteen weeks after treatment, CT shows significant anti-tumor effects. (D) Anterior planar image of pelvis at 48 h demonstrates focal uptake of 111In-epratuzumab in right pelvic side-wall disease seen (arrow) on baseline CT (E; arrows show bilateral tumor involvement) representing TP finding, but no definite tumor uptake in left pelvic side-wall disease seen on baseline CT (FN). (F) Significant improvement of both TP and FN lesions is shown on 16-wk follow-up CT image.

View larger version (101K): [in a new window]   FIGURE 7. Patient 1-9 is 54-y-old man with follicular NHL who was treated with 0.944 GBq (25.5 mCi) 90Y-epratuzumab (0.55 GBq/m2, 15 mCi/m2). Transaxial image of pelvic SPECT (A) and planar anterior 111In-epratuzumab image of pelvis (B) performed at 48 h after injection demonstrate tumor uptake in a right iliac node (arrows) that corresponds with baseline CT lesion (C, arrow). (D) Note marked improvement on follow-up CT 12 wk after 90Y-epratuzumab treatment.

View larger version (106K): [in a new window]   FIGURE 8. Patient 2-3 is 56-y-old man with aggressive NHL (follicular mixed) who previously had HDC with peripheral blood stem cell transplant 11 mo before receiving 90Y-epratuzumab. He was treated with 0.333 GBq (9 mCi) 90Y-epratuzumab (0.185 GBq/m2 or 5 mCi/m2). (A) Posterior planar image taken 1 h after 111In-epratuzumab illustrates positioning of left (outlined) and right kidney. At 24 h (B) and 48 h (C), uptake in left mass is seen to develop (arrow), whereas uptake in right mass could not be demonstrated. Four weeks after treatment, both left (D [baseline] and E [4-wk follow-up] CT) and right (F [baseline] and G [4-wk follow-up] CT) lesions had significant reductions in size, with complete disappearance of right renal mass and only small residual mass remaining on left side.