RT Journal Article SR Electronic T1 Tumor uptake of 64Cu-DOTA-trastuzumab correlates with HER2 gene amplification in patients with metastatic breast cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 49 OP 49 VO 57 IS supplement 2 A1 James Bading A1 Michael Press A1 Ivonne Villalobos A1 Paul Frankel A1 Jinha Park A1 Tri Tran A1 Mary Carroll A1 Erasmus Poku A1 Joshua Miles A1 David Colcher A1 Joanne Mortimer YR 2016 UL http://jnm.snmjournals.org/content/57/supplement_2/49.abstract AB 49Objectives Tumor uptake of 64Cu-DOTA-trastuzumab varies widely among patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (Mortimer,et al., JNM 2014; 55:23-29). We sought to determine the degree to which this observation reflects variation of HER2 gene amplification, a strong correlate of tumor HER2 expression (Slamon, et al., Science 1989;244:707-712). Methods Patient HER2 status at time of study was determined from biopsied tumor tissue and classified by standard criteria [HER2+: immunohistochemistry IHC 3+ or IHC 2+ and fluorescence in situ hybridization (FISH)-derived HER2-to-reference gene copy ratio > 2.0]. Patients with HER2+ (n=8) or HER2- (n=10) metastatic breast cancer who had not received anti-HER2 therapy for 蠅 2 mo were given trastuzumab i.v. (45 mg, to reduce liver uptake) prior to i.v. injection of 64Cu-DOTA-trastuzumab (364-551 MBq). PET-CT scans were obtained at 21-25 h (3-4 bed positions, 20 or 15 min each) over fields of view based on recent (&#8804; 17 d prior) 18F-FDG scans. Radiolabel uptake in lesions with maximum diameter on CT 蠅 15 mm (3-10 per patient) was measured as maximum voxel SUV (SUVmax). Residual tissue from tumor biopsies was assayed by FISH to determine average number of HER2 gene copies per tumor cell (<#HER2 copies/cell>). Results Intra-patient average SUVmax (<SUVmax>, range 3-16 g/mL) was positively correlated (r = 0.86, P < 0.001) with measured <#HER2 copies/cell> (range 2-28). The HER2+ group had higher average <SUVmax> than the HER2- group [9.1 ± 3.8 vs 4.9 ± 1.1 g/mL (mean ± SD); P <0.01], but <#HER2 copies/cell> accounted for more of the variance in <SUVmax> than did HER2 class (74 vs 42%). Although the two groups were well separated with respect to <#HER2 copies/cell>, two HER2+ patients had lower <SUVmax> than three of the HER2- patients. Furthermore, some HER2+ patients with very similar <#HER2 copies/cell> had widely different <SUVmax>, indicating that tumor uptake is not determined solely by HER2 expression. Conclusions Tumor uptake of 64Cu-DOTA-trastuzumab reflects binding to HER2 as early as 1 d post injection. Measurement of <#HER2 copies/cell> by FISH is a better predictor of trastuzumab uptake than standard HER2 classification. The wide range of 64Cu-DOTA-trastuzumab uptake among HER2+ patients correlates with variable tumor HER2 expression driven by variations in gene amplification. However, HER2 expression/gene amplification is not the only significant determinant of trastuzumab uptake. RESEARCH SUPPORT. DOD 1024511.