Biodistribution and pharmacokinetics of radiolabeled trastuzumab in HER2-positive metastatic breast cancer

Abstract

3063 Background: Trastuzumab combined with chemotherapy can induce remissions in HER2 positive metastatic breast cancer (MBC), but also cardiac dysfunction. The aim of this study is to evaluate whether scintigraphy using radiolabeled trastuzumab can predict cardiotoxicity, and identify tumor lesions and response. Methods: In an ongoing study, patients (pts) with HER2 positive MBC, suitable for Herceptin (d1, 8 and 15) plus paclitaxel (d1), underwent gammacamera imaging and blood sampling from 15 min to 7d after injection of 150 MBq 111In-DTPA-trastuzumab, prior to and after 4 therapy cycles. In known lesions (CT/ultrasound/Xray/bone scan), the degree of 111In-DTPA-trastuzumab tumor uptake was expressed as tumor/ background ratio (tumor vs. background uptake intensity) and as % injected dose index (tumor vs. total body (TB) counts). Results: Up to now, 11 pts have been enrolled. Plasma T½α was 14.7±6.97h, T½β 115.9±46.71h (n=8). Variable uptake in tumor lesions was present in all pts after 5 and 7d, starting from d1. At d1, tumor/background ratio was 2.0 (1.4–3.5), 0.7% TB (0.1–5.5%) uptake. At d7 these figures were 2.1 (1.7–9.3) and 0.9%TB (0.2–5.5%). One or multiple lesions were visualized in every pt, although not all known lesions. In 5 pts previously unknown lesions were found. Visualization of liver metastases was difficult (missed in 2/ 6 pts), due to high liver uptake (d5 24.3%, 17.4–33.6%). Uptake in organs such as, spleen and kidneys, and bloodpool activity decreased between d1 and 7, while tumor and liver uptake increased. Myocardial uptake occurred in 1 pt, who had cardiac arrhythmias prior to treatment. Conclusions: Preliminary results show that radiolabeled trastuzumab scintigraphy can identify HER2 positive tumor lesions, which may assist in identifying metastases and in predicting tumor response. Defining predictive value for cardiotoxicity and tumor response requires a larger pt number. This study continues to recruit. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Roche Bristol-Myers Squibb; Roche