Joanne E Mortimer1, James R Bading2, Jinha M Park3, Paul H Frankel4, Mary I Carroll2, Tri T Tran3, Erasmus K Poku5, Russell C Rockne4, Andrew A Raubitschek5, John E Shively6, David M Colcher5. 1. Department of Medical Oncology and Experimental Therapeutics, City of Hope, Duarte, California jmortimer@coh.org. 2. Department of Medical Oncology and Experimental Therapeutics, City of Hope, Duarte, California. 3. Department of Radiology, City of Hope, Duarte, California. 4. Department of Information Sciences, City of Hope, Duarte, California. 5. Department of Cancer Immunotherapy and Tumor Immunology, Beckman Research Institute of the City of Hope, Duarte, California; and. 6. Department of Immunology, Beckman Research Institute of the City of Hope, Duarte, California.
Abstract
The goal of this study was to characterize the relationship between tumor uptake of 64Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUVmax Average intrapatient SUVmax (<SUVmax>pt) was compared between HER2+ and HER2- patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median <SUVmax>pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients (P < 0.005 either day). The distributions of <SUVmax>pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease (P < 0.005 and 0.001, respectively, on days 1 and 2). Conclusion: By 1 d after injection, uptake of 64Cu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for 64Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.
The goal of this study was to characterize the relationship between tumor uptake of 64Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of humanepidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods:Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUVmax Average intrapatient SUVmax (<SUVmax>pt) was compared between HER2+ and HER2- patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median <SUVmax>pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients (P < 0.005 either day). The distributions of <SUVmax>pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease (P < 0.005 and 0.001, respectively, on days 1 and 2). Conclusion: By 1 d after injection, uptake of 64Cu-DOTA-trastuzumab in MBC is strongly associated with patientHER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for 64Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.
Authors: Joanne E Mortimer; James R Bading; David M Colcher; Peter S Conti; Paul H Frankel; Mary I Carroll; Shan Tong; Erasmus Poku; Joshua K Miles; John E Shively; Andrew A Raubitschek Journal: J Nucl Med Date: 2013-12-12 Impact factor: 10.057
Authors: Gary A Ulaner; David M Hyman; Dara S Ross; Adriana Corben; Sarat Chandarlapaty; Shari Goldfarb; Heather McArthur; Joseph P Erinjeri; Stephen B Solomon; Hartmuth Kolb; Serge K Lyashchenko; Jason S Lewis; Jorge A Carrasquillo Journal: J Nucl Med Date: 2016-05-05 Impact factor: 10.057
Authors: Richard Laforest; Suzanne E Lapi; Reiko Oyama; Ron Bose; Adel Tabchy; Bernadette V Marquez-Nostra; Jennifer Burkemper; Brian D Wright; Jennifer Frye; Sarah Frye; Barry A Siegel; Farrokh Dehdashti Journal: Mol Imaging Biol Date: 2016-12 Impact factor: 3.488
Authors: Katherine L Pogue-Geile; Chungyeul Kim; Jong-Hyeon Jeong; Noriko Tanaka; Hanna Bandos; Patrick G Gavin; Debora Fumagalli; Lynn C Goldstein; Nour Sneige; Eike Burandt; Yusuke Taniyama; Olga L Bohn; Ahwon Lee; Seung-Il Kim; Megan L Reilly; Matthew Y Remillard; Nicole L Blackmon; Seong-Rim Kim; Zachary D Horne; Priya Rastogi; Louis Fehrenbacher; Edward H Romond; Sandra M Swain; Eleftherios P Mamounas; D Lawrence Wickerham; Charles E Geyer; Joseph P Costantino; Norman Wolmark; Soonmyung Paik Journal: J Natl Cancer Inst Date: 2013-11-21 Impact factor: 13.506
Authors: Yu-Chuan Ou; Xiaona Wen; Christopher A Johnson; Daniel Shae; Oscar D Ayala; Joseph A Webb; Eugene C Lin; Rossane C DeLapp; Kelli L Boyd; Ann Richmond; Anita Mahadevan-Jansen; Marjan Rafat; John T Wilson; Justin M Balko; Mohammed N Tantawy; Anna E Vilgelm; Rizia Bardhan Journal: ACS Nano Date: 2020-01-02 Impact factor: 15.881
Authors: Ingrid J G Burvenich; Sagun Parakh; Adam C Parslow; Sze Ting Lee; Hui K Gan; Andrew M Scott Journal: AAPS J Date: 2018-03-08 Impact factor: 4.009
Authors: Farrokh Dehdashti; Ningying Wu; Ron Bose; Michael J Naughton; Cynthia X Ma; Bernadette V Marquez-Nostra; Philipp Diebolder; Cedric Mpoy; Buck E Rogers; Suzanne E Lapi; Richard Laforest; Barry A Siegel Journal: Breast Cancer Res Treat Date: 2018-02-13 Impact factor: 4.872