Gopal Subramanian

99mTc-Labeled Polyphosphate as a Skeletal Imaging Agent1

A new complex of 99mTc with a synthetic linear long-chain polyphosphate shows excellent potential as a skeletal imaging agent on the basis of preliminary animal tissue radio-assay and imaging studies. Skeletal metastases were demonstrated by rectilinear scanning and gamma camera imaging. The quality of the scans were comparable with those obtained with 18F.

Experimental and clinical trials of new 99mTc-labeled hepatobiliary agents.

Several new derivatives of lidocaine were synthesized and used to examine the intra- and extrahepatic bile ducts and gallbladder. Diisopropyl-IDA exhibited approximately twice the bile concentration of 131I-rose bengal during the first hour after injection. P-butyl-IDA also concentrates moderately well in the bile and has the added advantage of very low excretion into the urine (2%). It seems more effective than the other IDA derivatives at high bilirubin levels.

Experimental agents for skeletal imaging

Of the experimental bone scanningagents discussed in this section, we feel that three deserve the most emphasis: technetium polyphosphate complex, Dysprosium HEDTA, and Erbium HEDTA. None is entirely perfect. Dysprosium at present is extremely difficult to produce. All of these agents require a chemical preparation in the laboratory. The advantages of each far outweigh their disadvantages and merit more investigation as potential substitutes for the radionuclides currently used. in skeletal imaging. Economically they are competitive with the radionuclides now in use.

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

Abstract99mTc-hexamethylpropylene amine oxime d,1 diastereoisomer (HM-PAO), developed as a diffusible brain imaging agent, labels leukocyte suspensions in saline with an efficiency of 80% using 1–200 μg 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.

Experimental Models and Evaluation of Animal Data for Renal Radiodiagnostic Agents

After a new gamma-emitting radiodiagnostic agent is synthesized and its chemical structure defined, serial camera imaging following administration to experimental animals can quickly determine its major organ localization. Blood and plasma disappearance curves and urinary excretion at different time intervals are also measured. For renal agents, with negligible extrarenal concentration or excretion, a double exponential analysis of the plasma disappearance curve may be used to quantitate renal clearance, in dogs (Blaufox et al., 1963) or even in small animals like the rat (Blaufox et al., 1970). If a new agent appears promising for eventual human use, more detailed concentration values are required for various organs at different time intervals. These are generally obtained by direct tissue radioassay following the sacrifice of a series of animals. It is frequently rewarding to compare (by dual channel pulse height analysis) the distribution of a new agent with that of an older one with similar organ localization, simultaneously injected and labeled with a radionuclide of different gamma energy. These tissue concentration data from animals are essential to calculate preliminary radiation dose estimates, before administration to humans is considered.

Monoclonal antibody against human fibrin for imaging thrombi

The detection and localization of venous thrombi, most common in the lower extremities and pelvis, remain a major diagnostic problem in clinical medicine. Although radiographic venography with contrast medium is highly sensitive and specific, the injections are frequently painful, and reactions from large doses of intravenous contrast media of varying severity occur. In the search for a less invasive diagnostic procedure, gamma camera imaging has been tried frequently, using a number of radioactive agents, including fibrinogen (1), split fibrin products (2,3), streptokinase, urokinase, plasminogen, plasmin (4), tissue plasminogen activator, and labeled platelets (5). Labeled fibrinogen fragment E was successful in pigs (4), but apparently less successful in human trials. Labeled platelets have consistently localized thrombi less than 12 hours old and even up to one day old, but older thrombi encountered in clinical practice are localized poorly (3). In general, the results of radionuclide imaging for thrombus detection have been disappointing. To attempt to improve the efficacy of camera imaging, we have explored the use of a labeled monoclonal antibody against human fibrin in a canine model.

Present Trends and Future Directions in “Leukocyte Labeling”

Imaging with In-111-labeled leukocytes has become an established clinical method for the detection of focal inflammatory lesions in many medical centers but has been rejected by others because of the technical complexities of the labeling procedure. Gaining knowledge of the in vivo migratory pattern of the different leukocyte populations and subtypes in health and disease remains an important goal(1), particularly in the field of immunology. Techniques for examining the in vivo distribution of lymphocytes, monocytes and the eosinophils are still under development, and differences in migratory patterns of mononuclear subtypes remain to be explored. This paper attempts to summarize recent progress in the techniques of harvesting and labeling leukocytes and suggests possible directions for future research.

Localization of fresh experimental venous thrombi in rabbits using 99mTc-oxine-labeled autologous platelets.

99MTc-oxine-labeled autologous platelets were used to visualize fresh experimental venous thrombi in rabbits. Clots were formed by intravenous injection of suspended 1.3 micron iron particles while a magnet was positioned over a vein proximal to the injection site. Thrombi formed prior to and following platelet injection were visualized well.

The role of the radiochemist in nuclear medicine

The radiochemist plays a vital role in nuclear medicine. He can be useful as a professional scientist providing radiodiagnostic agents for routine clinical use, and if called upon he can run the in vitro and radioimmunoassay laboratory. As a teacher, he can make substantial contributions in training physicians and technologists in nuclear medicine, and as a researcher he can be valuable in developing new radiodiagnostic agents while working in close collaboration with physicians. At present, there is a shortage of these trained scientists, and colleges of health-related professions in major medical centers should institute programs to train these vitally needed professionals.

Radioactive Monoclonal Antibodies Against Cell Surface Antigens for Labeling Leukocyte Subpopulations

The ability to follow the kinetics and migration of various leukocyte populations, particularly with the oxine and tropolone lipophilic chelates of In-111, has contributed greatly to our expanding knowledge of cellular immunology in recent years (1, 2, 3, 4). In the cellular immune system, lymph nodes collect and process antigen from extracellular fluid — the peripheral nodes for superficial tissues and the spleen for blood-borne antigens. The gastrointestinal tract has its own lymphoid organs for processing ingested antigens — Peyer’s patches, appendix, tonsils and adenoids (5). Labeled T cells migrate preferentially to peripheral lymph nodes and B cells to the spleen and Peyer’s patches (6). This organ-specific homing is controlled by interaction between recirculating lymphocytes and endothelial cells of post-capillary high endothelial venules (HEV) through specific surface receptors, thereby directing the cells into the lymphoid organs. A greater localization of cytotoxic T cells than helper T cells has been observed in Peyer’s patches, but their localization is equal in peripheral nodes (7).