Human dosimetry and tumor kinetics of 111In CHX-A” DTPA trastuzumab in solid tumors using gamma-camera imaging

Objectives Trastuzumab (Herceptin™), targets HER2 on the surface of cancer cells and is used in the treatment of breast cancers that over-express HER2; however, it has also been demonstrated that other malignancies express HER2. Trastuzumab was radiolabeled with 111In via a CHX-A” DTPA bifunctional chelator (111In HER2) and human biodistribution studies were performed in patients with solid tumors. This imaging agent may be useful in determining tumors which may respond to Herceptin™, identifying metastases, monitoring treatment response or establishing dosimetry for future radioimmunotherapy.

Methods To date, 6 HER positive patients (tumor size >2.5cm) have undergone gamma-camera imaging (+/-SPECT/CT) at multiple time points following the i.v. injection of 4.8 mCi, (<200μg) 111In HER2. Normal organ time activity curves (TACs) were created and human dosimetry estimations were made using OLINDA. Tumor uptake was also measured.

Results The only adverse event observed was self limiting Gr1 taste disturbance. Dosimetry estimates showed the liver receiving the highest dose, 2.66rads/mCi, followed by the lower and upper large intestines (1.32 and 0.85rads/mCi, respectively). The ED was 0.47rem/mCi. All 6 patients enrolled to date were HER2 positive by FISH or IHC. Tumors were identified in all 6 patients and while tumor uptake peaked at 4 hr, T:B plateaued at 48-72 hr.

Conclusions The in vivo biodistribution of 111In HER2 in humans can be imaged without addition of cold Herceptin. Based on RDRC recommendations, 3.5 mCi/dose would permit three 111In HER2 imaging studies within 1 year