Permeability of cyst walls in vivo: investigations with radioactive tracers.
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In 7 rabbits the drainage of 99mTc-labelled Micro-colloid from the vitreous body of the eye was studied. In vivo measurements with an Anger-type camera were undertaken as well as in vitro measurements after dissection and excision of tissue-probes. From the data followed that indicator's elimination half-life from the vitreous body was on an average 7.8 hours. The drainage occurred partially along structures which are associated to the optic nerve. Furthermore drainage to the ipsilateral retrobulbar space and to the regional cervical lymph nodes, mainly to the bilateral deep cervical lymph nodes could be observed.
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In 7 rabbits the drainage from the subconjunctival space to the cervical lymph nodes was observed after subconjunctival injection of 99mTc-micro-colloid. Measurements of the activity distribution were made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after dissection with a sodium iodine crystal well counter (Clinimat-200, Picker). 6 hours after the injection into the subconjunctival space of the right eye an average of 53.7% of the applied activity had drained off. A significant accumulation of activity could constantly be registrated in the cervical lymph nodes. Its amount was generally up to 2.08% of the applied total activity per animal, with a large individual spreading. In detail, activity was found in all 7 cases in the right superficial cervical lymph node, in 5 cases moreover in the right mandibular lymph node, additionally in 2 animals in the right or left deep cervical lymph node respectively and in one animal as well in the right as in the left deep cervical lymph node. Besides, in all cases high activity was registered in the right retrobulbar and subconjunctival spaces just as in the right eye. A small activity in the right optic nerve could be pointed out in three of our seven cases.
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We describe the use of liposomes as a delivery system for radiopharmaceutical localization. Liposomes [99mTc-DTPA] were injected intravenously in mice and showed preferential uptake in the liver and spleen. There was a steady decline of activity in all organs, suggestive of destruction of liposomes with subsequent release of 99mTc-DTPA into the circulation. Alteration of uptake from liver to spleen, lung, and bone marrow was achieved by prior loading of the circulation with nonradioactive liposomes. The same effect was produced in dogs and demonstrated with scintigraphy. We also showed scintigraphically in dogs how 99mTc-DTPA, when administered entrapped in liposomes, follows the pattern of distribution of liposomes. Liposomes seem to be suitable carriers for radiopharmaceuticals. Further studies should show the possibility of directing liposomes to specific targets.
The field of nuclear medicine, defined as the application of radioactive tracers to medical diagnosis and treatment, has progressed significantly over recent years. At one time, only measurements of the concentrations of the radioactive tracers or other chemicals in blood, urine or other biologic material could be obtained at various intervals after the administration of a tracer or chemical. Therefore, prior to development of radiation detectors that reveal the distribution of radioactive tracers within the body, the function of the body could be studied only as a whole. It now is possible to study both regional and total body function by using the many radioactive tracers available and suitable imaging devices. By using the short-lived tracers (which have improved the quality of the images and reduced the radiation dose to the patient) and the recently developed scintillation camera, rapid dynamic studies of the course of the tracers through regions of the body may be performed, so that both spatial and temporal resolution is obtained. The use of computers has added a new dimension to the field of nuclear medicine. It is possible to improve greatly the quality of the information obtained. As a result, the regional distribution of radioactivity can be quantified and the changes that take place over a period of time in serial studies evaluated. Thus using a variety of radioactive tracers, each measuring a specific function, we can construct a mosaic of quantitative measurements of regional function. In this way, nuclear medicine may develop a body of coherent knowledge and become a clinical science as well as a collection of useful technics.
In contrast to "weightless" radioactive tracers, stable isotope tracers have nonnegligible mass and are naturally present in the system, and the measured variable is a ratio of two isotopic species. These features do not allow stable isotopic tracer data analysis using straightforward analogy with radioactive tracer approaches, even though this practice is common. In this study, we present kinetic variables, models, and measurements for the analysis and interpretation of stable isotope tracer data. Assumptions and mathematical techniques for modeling the data when perturbation is both nonnegligible and negligible are discussed. Emphasis is placed on the rich information content of the dynamic portion of a stable isotope tracer curve and on the role of compartmental and noncompartmental modeling approaches for its interpretation. A presumed and commonly used analogy between the radioactive specific activity and stable isotopic enrichment is shown to be incorrect. We show that the proper analogue of specific activity is the tracer-to-tracee molar ratio. This variable is not a directly measurable one, but a formula is derived that allows its computation from the data. A method for reconstructing the time course in blood of the concentration component due to endogenous synthesis is presented. This allows measurement of the extent of the perturbation in the case where a nonweightless tracer is used. Special attention is given to data analysis originating from a multiple tracer experiment, a configuration necessary for studying more complex systems, e.g., the kinetics of interacting substrates.
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Radioactive tracers are routinely used in investigation of the metabolism of apolipoprotein kinetics. Here, metabolic studies of apolipoprotein tracers labeled with radioiodine were analyzed to determine the absorbed radiation dose received by the subject. This analysis used compartmental modeling techniques to evaluate the radiation dose to various organs and the total body resulting from radioiodinated tracer injection. In this approach, we combined the published kinetic models of iodine and those of specific apolipoproteins. From the solution of the integrated compartmental models, residence times of the radiation in various source organs, in particular the thyroid, whole body, bladder, and red bone marrow, have been determined for the apolipoproteins apoA-I, apoA-II, very-low-density lipoprotein (VLDL)-apoB, and low-density lipoprotein (LDL)-apoB, each labeled with iodine 123, 133, 124, 131, 126, and 125. These tabulated values were used to calculate radiation doses to the different target organs. The thyroid is the organ that receives the largest dose of delivered radiation, and the importance of the duration of administration of iodine salts in blocking radiation to the thyroid is demonstrated. Optimal block times of 28 days for 131I and 42 days for 125I-labeled apolipoprotein tracers are proposed. When such a protocol is followed, the radiation dose to the thyroid and other organs is small by comparison to radiation doses allowed for workers whose occupation exposes them to radiation. The importance of frequent voiding to reduce the radiation dose to the bladder has also been demonstrated.
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