99mTc-labeled transferrin was prepared by reduction of99mTcO
; with stannous DTPA or stannous citrate followed by equilibration of the technetium chelate with human transferrin. The rate
of transfer of99mTc to transferrin in the presence of 0.015M citrate buffer was dependent on pH in the order pH 2.1> pH 7.2> pH 4.1> pH 5.9.
The incorporation rate was inversely proportional to the concentration of DTPA and citrate buffer. The replacement of citrate
buffer by acetate buffer or oxalate buffer reduced drastically the formation of99mTc-labeled transferrin at pH 4.1. The formation of99mTc-labeled transferrin prepared from the reduction of99mTcO
with stannous citrate was faster than that from the reduction with stannous DTPA in the presence of 0.015M citrate buffer
and pH 2.5. Equilibration of transferrin with99mTc-labeled pyrophosphate did not produce99mTc-labeled transferrin at pH 4.5. The ligand exchange labeling of99mTc to transferrin in 0.015M citrate did not cause appreciable denaturation of the protein at all pH values. This method also
enabled labeling of the protein in a low concentration (2.6·10−4 M) via tin reduction. Sequential external imaging of the99mTc-labeled transferrin in Sprague-Dawley rats bearing Walker-256 carcinosarcoma showed optimal tumor localization occurred
at 3 hr after injection. In spite of this,99mTc-labeled transferrin does not appear to be a suitable imaging agent because of the low tumor to blood ratio of99mTc (0.50±0.17) at 3 hr post injection. This is similar to that of6 7Ga-citrate (0.43±0.15%).