Figure 2.

Treatment with 4MU/HLX increases [⁸⁹Zr]Zr-DFO-trastuzumab accumulation in HER2-expressing JIMT1 tumor xenografts, an effect that is blocked with an excess of unlabeled trastuzumab. (A) Schematic diagram of JIMT1 tumor-bearing mice treated with 4MU/HLX and used in imaging and biodistribution studies with [⁸⁹Zr]Zr-DFO-trastuzumab. 4MU was orally administered (0.8 mg/g of mice) every day for 3 weeks. HLX was subcutaneously administered (10 units) every day in the third week. [⁸⁹Zr]Zr-DFO-trastuzumab (8.14−10.18 MBq, 80−100 μg of protein) was administered by tail vein injection on day 3 of the third week. (B) Representative MIP and coronal PET images and (C) biodistribution at 48 h p.i. of [⁸⁹Zr]Zr-DFO-trastuzumab in control and 4MU/HLX-treated athymic nude mice bearing subcutaneous JIMT1 breast tumors. Blocking experiments were performed by the administration of ⁸⁹Zr-labeled trastuzumab in the presence of a 40-fold molar excess of unlabeled trastuzumab. Data represent the mean ± SEM (n = 5 mice per group, *P < 0.05, **P < 0.01 based on a Student’s t-test and compared with the control; ^{$ $}P < 0.01 based on a Student’s t-test and compared with tumor treated with 4MU/HLX). Treatments were performed as represented in panel A. White arrows show the tumor region. MIPs, maximum intensity projection. %ID/g, percentage of injected dose per gram of tissue.