Tumor Uptake of 64Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer

Joanne E. Mortimer; James R. Bading; Jinha M. Park; Paul H. Frankel; Mary I. Carroll; Tri T. Tran; Erasmus K. Poku; Russell C. Rockne; Andrew A. Raubitschek; John E. Shively; David M. Colcher

doi:10.2967/jnumed.117.193888

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FIGURE 1.
Tumor uptake (SUV_max) of ⁶⁴Cu-DOTA-trastuzumab versus patient IHC/FISH score from biopsied tumor. Data are from ⁶⁴Cu-DOTA-trastuzumab PET/CT scans acquired 1 d (A and B) and 2 d (C and D) after injection. In A and C, the data for individual tumors (black dots) are grouped by patient and IHC/FISH score. Intrapatient means are represented by red horizontal lines. In B and D, SUV_max for individual lesions (open circles) are combined across patients and grouped by IHC/FISH score (n = number of tumors per group). Intragroup medians are represented as amplitudes of rectangular overlays; errors bars denote first and third quartiles. In both analyses, tumor uptake is generally higher for the HER2+ subgroups (3+ or 2+/FISH+) (P < 0.005). Relative variability of uptake was greater for HER2+ than HER2− group, both among (P < 0.001) and within (P < 0.05 on day 2) patients.
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FIGURE 2.
Examples of increased tumor uptake and tumor-to-nontumor contrast between 1 and 2 d after injection of ⁶⁴Cu-DOTA-trastuzumab. White and red arrows, respectively, denote tumors and blood pool as seen in transaxial PET/CT fusion images. Images on left are from a HER2+ (IHC2+/FISH+) patient. A (day 1) and C (day 2) show large metastasis in prevascular lymph node for which uptake was concentrated at tumor surface. Upper intensity threshold (white color) corresponds to SUV = 22 g/mL. At times of the 2 scans (24 and 48 h), measured SUV_max for tumor was 17 and 27 g/mL, respectively, whereas SUV for blood was 15 and 11 g/mL. Right-hand column depicts metastatic mass in right breast of a HER2− patient (IHC1+). Upper intensity threshold for images (white color) was set at SUV = 10 g/mL. SUV_max for tumor increased from 2.6 to 5.0 g/mL between day-1 (25 h after injection) (B) and day-2 (49 h after injection) (D) scans, whereas SUV for blood declined from 12 to 8.8 g/mL.
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FIGURE 3.
Examples of tumor visualization with ⁶⁴Cu-DOTA-trastuzumab PET/CT. Scan images are transaxial PET/CT fusion images with upper intensity thresholds (white color) corresponding to SUV = 10 g/mL. Patient depicted in A and B had recurrent disease after double mastectomy that was scored IHC1+. Scanning began 21 h after injection. Measured SUV_max was 6.9 g/mL for lesion in surface of right breast (red arrow) and 6.0 g/mL for mass beneath it (white arrow). Patient shown in C and D had widespread metastatic disease scored as IHC3+. Scanning, begun 25 h after injection, showed SUV_max of 7.0 g/mL in tumor at and near surface of left breast (arrows).

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TABLE 1

Patient Demographics and Clinical Characteristics

Characteristic	HER2+ (n = 11)	HER2− (n = 7)
Median age (y)	59 y (age range, 35–75 y)	61 y (age range, 40–71 y)
Hormone receptor and HER2 status of recurrent disease
ER and PR receptors
ER- and/or PR-positive	6
ER- and PR-negative	5
HER2
IHC1+
IHC2+	3
IHC3+	8
Prior HER2-directed therapy
None	3
Trastuzumab for metastasis	8 (79 d–36 mo)
Sites of metastatic disease measured for SUV_max
Bone	24
Lymph nodes	23
Liver	6
Lung	6
Other^*	2
Breast/chest wall^†	5
Tumor volume (cm³)^‡
Mean	5.8
SE	0.9

↵* Pulmonary effusion (HER2+) or body wall outside breast region.
↵† Breast or chest wall adjacent to breast.
↵‡ Volume within isocontour of ¹⁸F-FDG tumor image approximately matching boundary of CT correlate.
HER2 = human epidermal growth factor receptor 2; ER = estrogen receptor; PR = progesterone receptor; IHC = immunohistochemistry.