Abstract
1498
Objectives: To determine, the effect of radio labeled and un-labeled antibody in a mouse Lymphoma model of widely disseminated minimal residual tumor. We present an animal model by which we can follow tumor growth at a very early, visually-undetectable, stage of tumor growth using non-invasive optical imaging. Methods: One million cells/mouse of luciferase-transfected Raji Lymphoma cells using Lentivirus vector were injected i.v. to female CB-17 SCID mice. We serially monitored the bioluminescence intensity of the mice for 40 minutes after luciferine i.p injection using the Xenogen IVIS imaging system. We classified animals into three subgroups; 1) NT: non-treatment (n=11), 2) IT: Immunotherapy (Rituximab: total 200μg/mouse) (n=6) and 3) RIT: radio-immunotherapy (131I-Tositumomab: total 150μCi and 200μg/mouse) (n=6). Antibodies were injected i.p at 17 and 21 days after tumor injection, and bioluminescent signal were measured every other day up to 60 days after tumor injection. Results: Treatment effect was determined by the total 40 minute area under curve (AUC) of photon intensity, tumor signal doubling time in the whole body (day) after treatment, and overall survival rate. Animals were humanely euthanized at the time point of appearance of hind-leg paralysis. Some animals also died without hind-leg paralysis in the RIT animals, likely due to radio-toxicity. There was a significant difference in total AUC signal at day 27 between NT and RIT (p<0.05), and a small difference was seen between NT and IT (p=0.13). The signal doubling time after treatment of NT, IT and RIT was 2.42, 3.15 and 4.09 respectively. The longest survival time was seen in RIT treatment group. The average survival time of NT, IT and RIT was 29.8, 33.2 and 38.3 respectively in this pilot study. Conclusions: Tumor cell killing effect was higher in RIT than the IT group. Radio-toxicity occurred in this model and resulted in only modest improvement in overall survival rate in the RIT group. This lymphoma model proved to be a highly sensitive, robust tool for monitoring the early stage of disseminated tumor growth and was useful for evaluating the effects of radioimmunotherapy on unmeasurable disease.
- Society of Nuclear Medicine, Inc.