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Abstract
Background: The purpose of this study was to evaluate both the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer.

Methods: PET images at 1, 24, and 48 h after 296 MBq of 64Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors' and metastatic lesions' maximum standardized uptake value (SUVmax) was evaluated. The mean SUVmax (SUVmean) was evaluated in the other organs, including the blood pool, liver, kidney, muscle, spleen, bladder, and the lungs, as well as the bones. Moreover, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed based on feedback regarding adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration.

Results: 64Cu-NOTA-Trastuzumab PET images showed that the overall SUVmean values in each organ negatively correlated with time. The liver's average SUVmean values were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 h, 24 h, and 48 h after injection, respectively. The average SUVmean blood values were measured at 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 h, 24 h, and 48 h after injection, respectively. The SUVmax of HER2-positive tumors was relatively higher than HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 h after injection, respectively). Tumor-to-background ratios were higher in the HER2-positive tumors than in the HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq).

Conclusions: 64Cu-NOTA-Trastuzumab showed a specific uptake at the HER2-expressing tumors, thus making it a feasible and safe monitoring tool of HER2 tumor status in patients with breast cancer.

시간 경과에 따른 HER2 발현 PET/CT 영상 및 방사성의약품 섭취 차이를 나타내는 그래프

방사성의약품(Cu-64-NOTA-trastuzumab) 섭취 정도를 지표로 표기한 최대 표준화 섭취계수(SUVmax)가 HER2 양성 종양은 평균 8.6, HER2 음성 종양은 5.2로 낮게 측정됨

Affiliations

Inki Lee  1 , Ilhan Lim #  2 , Byung Hyun Byun  1 , Byung Il Kim  1 , Chang Woon Choi  1 , Sang-Keun Woo  3 , Kwang Il Kim  3 , Kyo Chul Lee  3 , Joo Hyun Kang  3 , Min-Ki Seong  4 , Hyun-Ah Kim  4 , Woo Chul Noh #  5 , Sang Moo Lim  1
1 Department of Nuclear Medicine, Korea Cancer Centre Hospital, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Korea.
2 Department of Nuclear Medicine, Korea Cancer Centre Hospital, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Korea. ilhan@kcch.re.kr.
3 Division of Applied RI, Research Institute of Radiological and Medical Sciences, Korea Institutes of Radiological and Medical Sciences, Seoul, Korea.
4 Department of Surgery, Korea Cancer Centre Hospital, Korea Institutes of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Korea.
5 Department of Surgery, Korea Cancer Centre Hospital, Korea Institutes of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Korea. nohwoo@kirams.re.kr.
# Contributed equally.