title: Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET.
abstract: Women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are candidates for treatment with the anti-HER2 antibody trastuzumab. Assessment of HER2 status in recurrent disease is usually made by core needle biopsy of a single lesion, which may not represent the larger tumor mass or other sites of disease. Our long-range goal is to develop PET of radiolabeled trastuzumab for systemically assessing tumor HER2 expression and identifying appropriate use of anti-HER2 therapies. The purpose of this study was to evaluate PET/CT of (64)Cu-DOTA-trastuzumab for detecting and measuring tumor uptake of trastuzumab in patients with HER2-positive metastatic breast cancer.
  
  
  METHODS
  Eight women with biopsy-confirmed HER2-positive metastatic breast cancer and no anti-HER2 therapy for 4 mo or longer underwent complete staging, including (18)F-FDG PET/CT. For 6 of the 8 patients, (64)Cu-DOTA-trastuzumab injection (364-512 MBq, 5 mg of trastuzumab) was preceded by trastuzumab infusion (45 mg). PET/CT (PET scan duration 1 h) was performed 21-25 (day 1) and 47-49 (day 2) h after (64)Cu-DOTA-trastuzumab injection. Scan fields of view were chosen on the basis of (18)F-FDG PET/CT. Tumor detection sensitivity and uptake analyses were limited to lesions identifiable on CT; lesions visualized relative to adjacent tissue on PET were considered PET-positive. Radiolabel uptake in prominent lesions was measured as maximum single-voxel standardized uptake value (SUVmax).
  
  
  RESULTS
  Liver uptake of (64)Cu was reduced approximately 75% with the 45-mg trastuzumab predose, without significant effect on tumor uptake. The study included 89 CT-positive lesions. Detection sensitivity was 77%, 89%, and 93% for day 1, day 2, and (18)F-FDG, respectively. On average, tumor uptake was similar for (64)Cu-DOTA-trastuzumab and (18)F-FDG (SUVmax and range, 8.1 and 3.0-22.5 for day 1 [n = 48]; 8.9 and 0.9-28.9 for day 2 [n = 38]; 9.7 and 3.3-25.4 for (18)F-FDG [n = 56]), but same-lesion SUVmax was not correlated between the 2 radiotracers. No toxicities were observed, and estimated radiation dose from (64)Cu-DOTA-trastuzumab was similar to (18)F-FDG.
  
  
  CONCLUSIONS
  (64)Cu-DOTA-trastuzumab visualizes HER2-positive metastatic breast cancer with high sensitivity and is effective in surveying disseminated disease. A 45-mg trastuzumab predose provides a (64)Cu-DOTA-trastuzumab biodistribution favorable for tumor imaging. (64)Cu-DOTA-trastuzumab PET/CT warrants further evaluation for assessing tumor HER2 expression and individualizing treatments that include trastuzumab.
authors: Department of Medical Oncology and Experimental Therapeutics, City of Hope, Duarte, California.
authors: Joanne E
authors: JE
authors: Mortimer
authors: James R
authors: JR
authors: Bading
authors: David M
authors: DM
authors: Colcher
authors: Peter S
authors: PS
authors: Conti
authors: Paul H
authors: PH
authors: Frankel
authors: Mary I
authors: MI
authors: Carroll
authors: Shan
authors: S
authors: Tong
authors: Erasmus
authors: E
authors: Poku
authors: Joshua K
authors: JK
authors: Miles
authors: John E
authors: JE
authors: Shively
authors: Andrew A
authors: AA
authors: Raubitschek
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D003301:Copper Radioisotopes; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography; D011874:Radiometry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C546788:64Cu-DOTA-trastuzumab; C508053:ERBB2 protein, human
keywords: 64Cu-labeled trastuzumab; HER2; breast cancer