Enhanced tumor imaging with pokeweed mitogen

Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance (both normal and aberrant) of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates (both normal and aberrant). Utilizing the B-16/C57BL/6 model, 7 days post-transplantation (which represents log phase growth of the tumor), 10 animals were imaged following an i.v. injection of 1–2 mCi 99mTc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1–2 mCi of 99mTc-human serum albumin (HSA). Twelve of these animals were given 10 μg of PWM i.p. at various intervals prior to the 99mTc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post- 99mTc-HSA injection. A 32-59% increase in the tumor-to-muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99mTc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99mTc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls. The use of PWM, and perhaps other structurally defined biomodulators may afford the opportunity to image aberrant tissue without the need for specialized tumor-specific preparations or may enhance the intrinsic properties of biologically-specific agents.