Jorge A Carrasquillo1,2, Patrick G Morris3,4, John L Humm5, Peter M Smith-Jones6,7, Volkan Beylergil6, Timothy Akhurst6,8, Joseph A O'donoghue5, Shutian Ruan6, Shanu Modi3, Clifford A Hudis3, Steven M Larson6,9,10. 1. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA - carrasj1@mskcc.org. 2. Center for Radioimmunotherapy and Theranostics, Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA - carrasj1@mskcc.org. 3. Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Department of Oncology, Beaumont Hospital, Dublin, Ireland. 5. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 7. Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA. 8. Peter MacCallum Cancer Center, Melbourne, Australia. 9. Center for Radioimmunotherapy and Theranostics, Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 10. Sloan Kettering Institute, New York, NY, USA.
Abstract
BACKGROUND: The current study aims to assess the safety, pharmacokinetics, feasibility, and reproducibility of immunoPET imaging with copper-64 (64Cu) trastuzumab. METHODS: An IV injection of 296-370 MBq/5 mg 64Cu-trastuzumab was administered between 1 to 4 hours after routine trastuzumab treatment. Whole-body PET scans were performed immediately post-injection and at 24 hours post-injection. Serial pharmacokinetics were performed. Of 11 patients (median age of 52; range of 31-61), 8 underwent a repeat study with 64Cu-trastuzumab to assess image and pharmacokinetic reproducibility. Patients were monitored for toxicity. RESULTS: Patients experienced no allergic reactions or significant adverse effects from 64Cu-trastuzumab. Eight patients successfully completed a repeat 64Cu-trastuzumab study, with acceptable reproducibility of both the biodistribution and pharmacokinetic clearance. Study 1 versus study 2 showed similar serum concentration post-injection (mean 42.4±7.8 %ID/L vs. 44.7±12.6 %ID/L) and similar T1/2 (single exponential 46.1 vs. 44.2 hours), P>0.5. The volume of distribution (median 2.50 L) was in the range reported for trastuzumab and close to the estimated plasma volume of 2.60 L. Of 11 patients, two had 64Cu-trastuzumab localization corresponding to known tumor sites - one in liver and one in breast. CONCLUSIONS: Preliminary results suggest that scanning with 64Cu-trastuzumab is feasible, safe, and reproducible. Tumor uptake of 64Cu-trastuzumab was observed, but tumor detection exhibited low sensitivity in this study in which imaging was performed in the presence of trastuzumab therapy.
BACKGROUND: The current study aims to assess the safety, pharmacokinetics, feasibility, and reproducibility of immunoPET imaging with copper-64 (64Cu) trastuzumab. METHODS: An IV injection of 296-370 MBq/5 mg 64Cu-trastuzumab was administered between 1 to 4 hours after routine trastuzumab treatment. Whole-body PET scans were performed immediately post-injection and at 24 hours post-injection. Serial pharmacokinetics were performed. Of 11 patients (median age of 52; range of 31-61), 8 underwent a repeat study with 64Cu-trastuzumab to assess image and pharmacokinetic reproducibility. Patients were monitored for toxicity. RESULTS: Patients experienced no allergic reactions or significant adverse effects from 64Cu-trastuzumab. Eight patients successfully completed a repeat 64Cu-trastuzumab study, with acceptable reproducibility of both the biodistribution and pharmacokinetic clearance. Study 1 versus study 2 showed similar serum concentration post-injection (mean 42.4±7.8 %ID/L vs. 44.7±12.6 %ID/L) and similar T1/2 (single exponential 46.1 vs. 44.2 hours), P>0.5. The volume of distribution (median 2.50 L) was in the range reported for trastuzumab and close to the estimated plasma volume of 2.60 L. Of 11 patients, two had 64Cu-trastuzumab localization corresponding to known tumor sites - one in liver and one in breast. CONCLUSIONS: Preliminary results suggest that scanning with 64Cu-trastuzumab is feasible, safe, and reproducible. Tumor uptake of 64Cu-trastuzumab was observed, but tumor detection exhibited low sensitivity in this study in which imaging was performed in the presence of trastuzumab therapy.
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