title: Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer.
abstract: We performed a feasibility study to determine the optimal dosage and time of administration of the monoclonal antibody zirconium-89 ((89)Zr)-trastuzumab to enable positron emission tomography (PET) imaging of human epidermal growth factor receptor 2 (HER2)-positive lesions. Fourteen patients with HER2-positive metastatic breast cancer received 37 MBq of (89)Zr-trastuzumab at one of three doses (10 or 50 mg for those who were trastuzumab-naive and 10 mg for those who were already on trastuzumab treatment). The patients underwent at least two PET scans between days 2 and 5. The results of the study showed that the best time for assessment of (89)Zr-trastuzumab uptake by tumors was 4-5 days after the injection. For optimal PET-scan results, trastuzumab-naive patients required a 50 mg dose of (89)Zr-trastuzumab, and patients already on trastuzumab treatment required a 10 mg dose. The accumulation of (89)Zr-trastuzumab in lesions allowed PET imaging of most of the known lesions and some that had been undetected earlier. The relative uptake values (RUVs) (mean +/- SEM) were 12.8 +/- 5.8, 4.1 +/- 1.6, and 3.5 +/- 4.2 in liver, bone, and brain lesions, respectively, and 5.9 +/- 2.4, 2.8 +/- 0.7, 4.0 +/- 0.7, and 0.20 +/- 0.1 in normal liver, spleen, kidneys, and brain tissue, respectively. PET scanning after administration of (89)Zr-trastuzumab at appropriate doses allows visualization and quantification of uptake in HER2-positive lesions in patients with metastatic breast cancer.
authors.affiliation: Department of Hospital and Clinical Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: E C
authors.initials: EC
authors.lastname: Dijkers
authors.forename: T H
authors.initials: TH
authors.lastname: Oude Munnink
authors.forename: J G
authors.initials: JG
authors.lastname: Kosterink
authors.forename: A H
authors.initials: AH
authors.lastname: Brouwers
authors.forename: P L
authors.initials: PL
authors.lastname: Jager
authors.forename: J R
authors.initials: JR
authors.lastname: de Jong
authors.forename: G A
authors.initials: GA
authors.lastname: van Dongen
authors.forename: C P
authors.initials: CP
authors.lastname: Schröder
authors.forename: M N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D061067:Antibodies, Monoclonal, Humanized; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D011868:Radioisotopes / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology; D000068878:Trastuzumab; D015040:Zirconium / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011868:Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D015040:Zirconium; C508053:ERBB2 protein, human