⁶⁴Cu-DOTA-Trastuzumab PET Imaging in Patients with HER2-Positive Breast Cancer

Abstract

The purpose of this study was to determine the safety, distribution, internal dosimetry, and initial human epidermal growth factor receptor 2 (HER2)-positive tumor images of 64 Cu-DOTA-trastuzumab in humans. Methods: PET was performed on 6 patients with primary or metastatic HER2-positive breast cancer at 1, 24, and 48 h after injection of approximately 130 MBq of the probe 64 Cu-DOTA-trastuzumab. Radioactivity data were collected from the blood, urine, and normal-tissue samples of these 6 patients, and the multiorgan biodistribution and internal dosimetry of the probe were evaluated. Safety data were collected for all the patients after the administration of 64 Cu-DOTA-trastuzumab and during the 1-wk follow-up period. Results: According to our results, the best timing for the assessment of 64 Cu-DOTA-trastuzumab uptake by the tumor was 48 h after injection. Radiation exposure during 64 Cu-DOTA-trastuzumab PET was equivalent to that during conventional 18 F-FDG PET. The radioactivity in the blood was high, but uptake of 64 Cu-DOTA-trastuzumab in normal tissues was low. In 2 patients, 64 Cu-DOTA-trastuzumab PET showed brain metastases, indicative of blood-brain barrier disruptions. In 3 patients, 64 Cu-DOTA-trastuzumab PET imaging also revealed primary breast tumors at the lesion sites initially identified by CT. Conclusion: The findings of this study indicated that 64 Cu-DOTA-trastuzumab PET is feasible for the identification of HER2-positive lesions in patients with primary and metastatic breast cancer. The dosimetry and pharmacologic safety results were acceptable at the dose required for adequate PET imaging.

Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2

“…In both studies, the best time for imaging was 48 h after tracer injection. However, the results were different; the coinjection of 45 mg of trastuzumab enabled better visualization of liver metastases (35), whereas the results obtained with the administration of only the radiotracer were suboptimal because of a higher liver background (34). Interestingly, both studies compared 64 Cu-trastuzumab PET/CT with 18 F-FDG PET/CT, with a maximum of 13 d in between, and showed that some lesions could be detected only with 64 Cu-trastuzumab PET/CT.…”

“…The study also highlighted the importance of the mass of administered protein, concluding that in trastuzumab-naive patients, a higher mass of (nonradiolabeled) trastuzumab (50 mg) enabled better distribution of the tracer into the metastatic lesions. In addition, trastuzumab was also labeled with 64 Cu in studies of both early and advanced HER2-positive BC (34,35). In both studies, the best time for imaging was 48 h after tracer injection.…”

Multiparametrische und molekulare Bildgebung von Brusttumoren mit MRT und PET‑MRT

“…In ersten Tierexperimenten bewiesen Smith-Jones et al [61] sowohl die Mög-lichkeit der nichtinvasiven Messung der HER2-Expression mit einem 68 Ga-markierten Fragment von Trastuzumab ll als auch die therapieinduzierte Ände-rung der HER2-Expression. In ersten klinischen PET-CT-Studien mit 64 Cu-DOTA-Trastuzumab konnte die 64 Cu-DOTA-Trastuzumab-PET-CT sowohl den Primärtumor als auch Metastasen mit hoher Sensitivität detektieren und hat somit das Potenzial, HER2-zielgerichtete Therapiestrategien zu optimieren [62].…”

Role of targeted therapy in the treatment of HER-2-positive breast cancer brain metastases

“…Однако рост опухоли в ГМ, а также последствия нейрохирургических вмешательств и об-лучения мозга могут нарушить гематоэнцефалический барьер и «открыть» доступ для системных препаратов в опухоль. Эта концепция была подтверждена в ряде исследований [26,27]. Кроме того, несколько клини-ческих исследований показали, что сочетание химио-терапии с трастузумабом повышает выживаемость даже после развития метастазов в ГМ [28,29].…”