Thrombus imaging with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its F(ab')2 and Fab fragments.

We have previously reported successful imaging of fresh (2-4 hr old) and aged (1-5 days old) canine thrombi with 131I-labeled intact monoclonal antibody (MAb) specific for fibrin. We now report thrombus imaging with 131I-labeled F(ab')2 and Fab and 111In-labeled intact MAb, F(ab')2, and Fab. Indium-111-labeled F(ab')2 proved to be the best imaging agent due to less nonspecific binding in the liver than whole IgG. Image quality was improved by the higher administered dose permissible with 111In and its better physical characteristics for imaging, compared to 131I. Immunofluorescence of fresh human histologic sections showed intact MAb and F(ab')2 binding to thrombi, pulmonary emboli, and atherosclerotic plaques, strengthening the feasibility of clinical thrombus imaging.

99mTc-HM-PAO for leukocyte labeling--experimental comparison with 111In oxine in dogs.

99mTc-hexamethylpropylene amine oxime d,l diastereoisomer (HM-PAO), developed as a diffusible brain imaging agent, labels leukocyte suspensions in saline with an efficiency of 80% using 1-200 micrograms quantities. In dogs, the recovery and survival of reinjected cells in the bloodstream resemble those of 111In-oxine labeled cells at least for several hours. Images in control animals at 18 h show the spleen, liver, marrow, and bladder, minimal pulmonary activity and some gastrointestinal activity. Induced E. coli abscesses and joint inflammatory lesions in dogs are shown on 18 h images. This complex appears promising as an agent for abscess detection in humans. However, strict quality control of this agent is necessary, and it must be used immediately after the 99mTc complex is formed for labeling cells.

Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA.

Dextrans with average molecular weights of 5,000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected [99mTc]DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5,000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect.

Technetium-99m DADS complexes as renal function and imaging agents: II. Biological comparison with iodine-131 hippuran.

To find a 99mTc agent with a high renal extraction efficiency similar to [131]hippuran, 21 analogs of DADS were labeled and evaluated. Preliminary screening by serial gamma camera imaging in rabbits showed that most analogs had a higher liver uptake and/or slower renal clearance, than hippuran. Three agents (P-DADS, AP-DADS, and CAP-DADS), exhibiting a relatively rapid blood clearance and lower liver uptake in the rabbit, were studied in greater detail in comparison with hippuran and CO2-DADS-A, the best analog to date. In the rat, the plasma clearance of the four DADS analogs was slower than that of hippuran. In rats with tubular damage induced by cisplatin, the difference in renal retention at 1 hr compared to controls was much greater with hippuran than with the DADS compounds. In the dog, there was marked hepatic retention of the four DADS compounds. In volunteers, serial posterior images obtained with these [99mTc]DADS complexes showed significant hepatic as well as renal activity. The 1-hr plasma clearance and urinary excretion were much lower than with simultaneously injected hippuran. Although these 99mTc agents are satisfactory for imaging the kidneys, they closely mimic the biodistribution of hippuran only in the rabbit, and not in the rat, dog, or man.

N,N'-bis(S-benzoylmercaptoacetamido) ethylenediamine and propylenediamine ligands as renal function imaging agents. I. Alternate synthetic methods.

A new method was developed to synthesize tetradentate ligands containing the N,N'-bis(S- benzoylmercaptoacetyl ) ethylenediamine and propylenediamine moieties (DADS compounds). Methods are also represented with which to synthesize some of the positional isomers of the above compounds. These isomers represent a new class of compounds. A total of 21 different compounds were prepared. These will be used in an effort to establish a relationship between structure and renal imaging properties.

New diphosphonate compounds for skeletal imaging: comparison with methylene diphosphonate.

Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications.

A new formulation of Tc-99m minimicroaggregated albumin for marrow imaging: comparison with other colloids, In-111 and Fe-59.

The biodistributions of five Tc-99m colloids were compared with the 24-hr distributions of Fe-59 and In-111 in dogs by direct radioassay 1 hr after intravenous injection. One formulation of Tc-99m minmicroaggregated albumin (particle size 30-100 mn), produced the highest marrow concentration, approximately six times that of Tc-99m sulfur colloid, with similar blood, and liver concentrations and a lower splenic uptake. Nevertheless, the best colloid marrow uptake was lower than the 24-hr value for In-11 and much lower than that for Fe-59. The marrow concentration of minimicroaggregated albumin was also higher than that of sulfur colloid in rats at 30 min after injection. The principal disadvantage of Tc-99m antimony sulfide colloid was its slow blood clearance. Clinical evaluation of Tc-99m minimicroaggregated albumin for marrow imaging appears warranted, although its hepatic activity will obscure overlying and immediately adjacent marrow.