Imaging of lymph node uptake after intravenous administration of indium-111 metalloporphyrins.

Indium-111- (111In) labeled tetra (N,N,N-trimethylanilinium) porphyrin (TTAP), tetra (N-methyl-4-pyridyl)porphyrin (TMPyP), and tetra(4-sulfonatophenyl)porphyrin (T4SPP) were synthesized and lymph node uptake was measured in animals after intravenous administration. In rats [111In] TTAP had maximum lymph node to muscle uptake ratios which averaged 85:1 between 24 and 48 hr postinjection. Total lymph node uptake was nearly 1% at that time. Lymph nodes in rabbits were clearly visualized by gamma scintigraphy at 48 hr after i.v. injection of labeled TTAP. These results suggest that 111In-labeled TTAP may be a prototype for the development of a class radiopharmaceuticals which permits visualization of lymph nodes after i.v. administration.

Radioimmunodetection of human tumor xenografts by monoclonal antibodies.

Mouse IgG2a monoclonal antibodies with specific binding reactivity in vitro to human tumors of the gastrointestinal tract were radioiodinated and injected into immunosuppressed mice xenografted with human colon carcinoma tumors. The antibodies preferentially localized in tumor tissue compared to normal mouse tissue, as determined by differential tissue counting of radioactivity. Preferential antibody localization in tumor tissue was greatly enhanced when F(ab')2 fragments of the antibodies were used, and the fragments localized specifically only in those tumors that bind the antibodies in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus monoclonal antibody of the same isotype as the specific antibody did not localize in tumors. Tumors could be located by whole-body gamma-scintigraphy with radiolabeled specific antibody F(ab')2 fragments without background subtraction.

Synthesis and evaluation of an 111In-labeled porphyrin for lymph node imaging.

111In-labeled tetra(4-N-methylpyridyl)porphyrin was investigated as a possible lymph node imaging agent. A clinically feasible method for the preparation of this radioactive pharmaceutical was developed from experiments with the synthesis and characterization of the unlabeled complex. The in vivo distribution of the compound in Wistar rats was determined as a function of time. Favorable lymph node-blood, lymph node-muscle, and specific lymph node-surrounding tissue ratios were obtained.

Electrophoretic determination of charge on carrier-free 99mTc-labeled complexes.

A new method for determining the charge on carrier-free 99mTc-labeled complexes is described. This method and mixed-ligand experiments were used to determine if the charge on the technetium 99m complex of N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (I) is - 1 and if the ligand to technetium ratio in the complex is 2:1. The preparation of an iodinated analog (II) of I and its 99mTc-labeled complex is described, as is the biodistribution of the 99mTc-labeled complex in mice. The synthesis of the 51Cr(III)- and 57Co(III)-labeled complexes also are described. The net biliary excretion in mice of both the 99mTc- and 51Cr-labeled complexes of II was significantly greater than that of the 99mTc-labeled complex of I.