Development of a spleen human B-cell lymphoma model in mice and characterization of response to chemotherapy

Objectives The vascular network and microenvironment in a splenic model are potentially more comparable to the human disease than subcutaneous tumors. Therefore, we aimed to establish and characterize a spleen tumor model and to evaluate chemotherapy induced metabolic response.

Methods A small piece (1mm³) of a subcutaneous xenograft tumor (Daudi cells) was transplanted in the spleen of 18 SCID mice. After 24d 15 mice out of 18 developed a measurable splenic tumor (0.4 cm³ to 2 cm³). Sequential ¹⁸F-FDG-PET over 6d were acquired in 8 mice. Five were treated with adriamycin (7 mg/kg) and cyclophosphamide (90 mg/kg). Additionally ^99mTc-(CO)₃-hAnxV was administered in another group of treated (n=4) and non-treated (n=3) tumor mice to investigate the potential to assess therapy response 1 day after treatment. Results were correlated to histological analysis (TUNEL).

Results The splenic tumors were highly ¹⁸F-FDG-avid (SUV_mean= 3.43 ± 0.6). ¹⁸F-FDG uptake decreased slightly (-15 %) 1d after treatment (SUV_mean= 2.9 ± 0.29). After 6d a significant decrease (-66 %) was measured (SUV_mean= 1.18 ± 0.84). ^99mTc-(CO)₃-hAnxV tumor uptake significantly increased 1d after treatment (0.79±0.15 % I.D./g) compared to non treated tumors (0.34±0.1 % I.D./g) correlating with the increased amount of apoptotic cells (+118 %).

Conclusions We developed a new tumor model which may advance preclinical assessment of new diagnostic and therapeutic strategies. A significant metabolic response was seen 6d after therapy. Apoptosis imaging gives the possibility to perform very early therapy assessment.