64CU-DOTA-TRASTUZUMAB-PET IMAGING IN PATIENTS WITH HER2-POSITIVE BREAST CANCER

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Abstract

Background

Targeting of HER2 with trastuzumab (T) is a well-established strategy in the metastatic and adjuvant setting in HER2-positive breast cancer (HER2-BC). Although the HER2 expression status is routinely determined using immunohistochemistry or fluorescence in situ hybridization, technical problems can arise when lesions are poorly accessible. The HER2 expression status can vary during the course of the disease, and there can be discordance in HER2 expression across tumor lesion even in the same patients. Noninvasive HER2 imaging is crucial to solve these problems. Previous imaging using 111In or 89Zn- trastuzumab produced high radiation exposure to patients by their long half life (=67.9 and 78.4 h) and low resolution image. Half life of 64Cu is 12.7 h. We carried out a feasibility study of the 64Cu-1,4,7,10- tetraazacylododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)-T to perform PET imaging in patients with HER2-BC.

Method

Patients with HER2-BC received 150 MBq of 64Cu-DOTA-T and underwent PET scan 1, 24 and 48 h after the injection. Six patients were evaluated internal dosimetry by collecting radioactivity data of blood and normal tissue in each time point from PET study, and radiation exposure by collecting clothes, linen and urine to test feasibility for outpatients.

Results

Fifteen patients who received T therapy were enrolled in the ‘first in human’ trial. All patients had no severe toxicity. Radiation excretion evaluating clothes, linen, were within the range of background level. The radiation exposure of 64Cu-DOTA-T was equivalent to that of conventional 18F-FDG-PET. The distribution of the liver, kidney, spleen, and blood vessel was 2–8 SUV, and uptake in other normal tissue was low. At visual examination, in two patients, brain metastases were clearly visualized by 64Cu-DOTA-T-PET, suggesting that there are disruptions of the blood-brain barrier at the site of the brain metastases. The sternum bone metastasis was well visualized and quantitatively monitored according to the response by T. Primary breast cancers, lymph node metastases and lung metastases could also be well visualized at the lesion indentified by CT.

Conclusion

64Cu-DOTA-T-PET was the feasible test even for outpatients and provides specific and high-resolution image in HER2-positive lesion.

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