Cellular mechanisms of protection and repair induced by radiation exposure and their consequences for cell system responses.

The complex biological systems that constitute living organisms operate at various levels of organization, from the atomic-molecular to the cellular to the organ-organism level. The response of an organism to disturbances that are detrimental to structure and function generally begin at the level of organization where the primary injury has occurred. Detriment that occurs from simultaneous or sequential, or single or multiple interactions at a relatively low level of organization tends to be transferred to higher levels. However, at each level of organization there is a given probability of such detriment being removed according to the tolerance to injury that is peculiar to that level. There is thus a direct relationship between the frequency of injurious events at a lower level of organization, and the degree of structural complexity of the system at the high level at which such detriment is eventually manifested. The extent of structural disruption at any given level determines the degree of functional failure at that level. In the exposure of tissue to ionization radiation, the primary injury begins with energy deposition events (tracks or hits) consisting of many ionizations and excitations in localized clusters of submicroscopic dimensions at the atomic-molecular level of organization within the cell, and the cell is affected as a whole. The cell is the elementary unit of life and the sum of the individual cell responses determines the response of the tissue and the organism. Individual cell responses are nevertheless found to differ in type and degree depending on the absorbed dose. With decreasing values of absorbed dose to the tissue, the probability of a cell being hit by an energy deposition event decreases linearly. At very low values of absorbed dose to tissue, only a fraction of the total cell population experiences single hits and these are of different sizes. The size distribution or spectrum of these hits is invariant, independent of their total number over a considerable range at low-dose levels and is determined only by the type and quality of the given radiation. The probability that a hit cell will suffer a given detriment such as a chromosomal aberration, gene mutation or death has been shown to increase in a sigmoid fashion with increasing hit size.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation hormesis. Its emerging significance in medical practice.

Because of the strong scientific evidence in support of radiation hormesis, we can no longer ignore this concept. There is, however, need for additional, carefully documented investigations in selected biological systems exposed to LLIR if the matter of radiation hormesis is to be settled once and for all. This need should be addressed without delay, as the matter of benefits derived from LLIR exposure could have major economic and epidemiologic implications. If radiation hormesis becomes firmly established, the requirements for LLIR protection might be relaxed, leading to a sizable cost saving, and the fear of nuclear energy should abate. If this happens, the evergrowing problems associated with energy production from fossil fuels on the one hand and the continued improvements in nuclear reactor technology on the other, will force a world-wide reassessment of risks and benefits associated with nuclear energy. Furthermore, as discussed herein, the major source of exposure from background radiation comes from the inhalation of radon gas. The very high cost associated with effective radon abatement would lead to an abandonment of this mitigation effort so that the limited funds available to improve public health world wide could be used more effectively elsewhere. Thus, we conclude that the time is now to consider eliminating the concept of the radiation paradigm from scientific thinking. We must not continue to unequivocally accept the propositions that 1) all radiation is harmful and 2) that the health effects of LLIR may be directly inferred by scaling down from known deleterious high-dose effects, in as much as there is no scientific basis for an agent not to cause multiple effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Nuclear medicine in the evaluation of organ transplants with special reference to heart and lung.

Organ transplantation has become routine in many hospitals throughout the world. Nuclear medicine techniques have played a significant role in the success of these programs through measurements of blood flow and function in these grafts, as well as assessments of infection and rejection. This paper emphasizes the present status of radiotracer methodology for evaluating heart and heart/lung transplants and also includes a brief summary of the development of nuclear medicine studies of other transplants.

Radioiodine therapy in thyrotoxicosis.

One hundred and two patients (81 females, 21 males) suffering from thyrotoxicosis as diagnosed clinically and confirmed by laboratory investigations including the estimation of thyroid hormones in blood were treated with radioiodine (I-131) at the University of Minnesota Hospital between 1976 and 1986. Nine (9%) patients needed two and 3 (3%) patients needed three therapeutic doses of I-131. The age range of the patients was 17-82 years (mean 43, SD 17). The doses of I-131 administered ranged from 3.9 to 100 mCi (mean 13.7). Twenty of these patients received a relatively high dose from 20 to 100 mCi. The others were given smaller calculated doses based on radioiodine uptake and thyroid size is determined by palpation and nuclear scans. Of the 73 patients for whom follow-up information was available, 66 (90%) eventually became hypothyroid as judged by clinical criteria. These data also suggest that the incidence of hypothyroidism is quite independent of the dose (microCi/g thyroid) administered.

Technetium-99m sulfur colloid spleen imaging following partial pancreatectomy and splenic artery and vein resection.

We retrospectively studied the records and [99mTc]sulfur colloid (TSC) spleen studies of 38 patients who underwent distal pancreatectomy with splenic artery and vein resection for donation to HLA-compatible relatives. The spleens in immediate postoperative TSC studies were normal in 11% of cases, showed no uptake in 16%, showed diffusely decreased uptake in 50%, and showed focal defects in 26%. Twenty of the patients, all with abnormal initial TSC studies, had repeat studies 2 wk to 3 yr later; 15% showed no change, 35% showed some improvement, and 45% became normal. One of six patients with no TSC uptake required splenectomy 2 days after pancreatectomy for splenic infarction. These data suggest that the spleen usually survives splenic artery and vein resection. Absent splenic TSC uptake raises the possibility of splenic infarction.

Positron emission tomography (PET): a unique approach for the imaging of in vivo metabolism.

Positron Emission Tomography (PET) is a new diagnostic imaging modality which will be available for the study of patients in the greater Nebraska area beginning mid year 1989. This technology will provide unique information on regional function and blood flow in a variety of body organs. Our emphasis will be placed on the identification of the viability of heart muscle in patients suffering a myocardial infarction or following thrombolysis who are being considered for a bypass procedure or angioplasty. We will also use PET to identify epileptic foci and to aid in the diagnosis of Alzheimer's disease, and for the assessment of the efficacy of various treatments of brain and other organ tumors. Despite the relatively high fixed costs of PET, we are confident that the unique information provided by this technology will prove not only to be effacacious but cost effective as well. Thus reimbursement through medical insurance programs, including Medicare, is expected to occur for those studies identified above. Likely coverage for additional PET procedures, particularly in the evaluation of psychiatric disorders, will occur after efficacy and cost effectiveness of these studies have been demonstrated.

Improved prediction of thyroid lobar mass from parameters obtained by routine thyroid scintigraphy.

Estimation of thyroid mass both from parameters derived from thyroid scintigraphy and clinical palpation for purposes of therapeutic dosimetry has not been tested for accuracy. To more precisely determine thyroid mass 90 thyroid lobes from 45 autopsies without history of thyroid disease were studied. Specimens were dissected free of nonthyroidal tissue and assessed for volume, maximum depth (D), width (W), length (L) and mass (M). Using a linear regression model and applying known lobar depth, the most accurate formula to predict true lobar mass (in grams) was 4.9D + 0.07L2W-2.3 (in cms). Length and width would be obtainable in vivo from routine scintigraphic measurements (in cm) and depth would be most accurately determined by ultrasound. For most clinical circumstances where lobar depth is unknown we found the best formula for mass (g) to be 0.1L2W (in cm).

Exercise-induced muscle uptake of technetium-99m MDP.

Intense muscle localization of Tc-99m MDP to upper extremity musculature was noted three days following weight lifting exercises. This phenomenon is due to an unknown mechanism although several causative factors have been suggested.

Comparison of the biodistribution of manganese-54 DTPA and gadolinium-153 DTPA in dogs.

The biodistribution of [54Mn]DTPA and [153Gd]DTPA dimeglumine were investigated and compared following i.v. administration to fasting anesthetized dogs. Unlike most previously reported metal ion-DTPA complexes, [54Mn]DTPA showed high uptakes in several organs including the liver, bile, pancreas, bowel, and kidney. This uptake was independent of the pH of the injected solution. Accumulation in these organs suggests a potential role for [Mn]DTPA as a paramagnetic contrast agent for NMR imaging. With the exception of the kidneys, [153Gd]DTPA showed no evidence of tissue specific uptake over the course of 4 hr, consistent with it being an extracellular ion that is cleared by glomerular filtration.

Functional imaging of the heart.

The generation of functional images from the time-activity curves of individual pixels in the gated blood-pool study has become a routine part of most nuclear medicine computer systems. These images have the advantage of extracting useful functional information from the entire study and presenting it in an easily interpretable format. One can rapidly examine them, especially the phase and amplitude images, to seek out potential abnormalities of contraction and conduction. These are not designed to be "stand alone" images and correlation with the remainder of the study, including the cine display, is required. In addition to their use in assessing abnormalities of either ventricular chamber, they also have been shown to be useful in delineating atrioventricular borders in both the left and right sides of the heart. This facilitates definition of regions of interest for the calculation of ejection fractions. These images are produced at no increased expense or inconvenience to the patient and therefore should always be evaluated.

Aerosol penetration ratio: a new index of ventilation.

Superimposition of nuclear medicine scintigrams and standard radiographs provides a unique opportunity for merging functional information intrinsic to nuclear medicine images with the high resolution anatomic detail of radiographs. A newly developed image processing system allows the merging of two separate films of greatly varying sizes to form a single composite image. Subsequent quantitative analysis of the composite image may be performed. Using the superimposition technique, [99mTc]DTPA aerosol ventilation scans (4.5 X 4.5 cm) were superimposed upon chest radiographs (35.6 X 43.2 cm) in 17 cystic fibrosis (CF) patients. Subsequent quantification of the area of nuclear scan ventilation and the radiographic lung area was then performed. A new quantitative radiologic index of ventilation, the aerosol penetration ratio (APR), was defined. Linear correlation of aerosol penetration ratio with residual volume (RV) as percent of total lung capacity (TLC) measured by body plethysmography was good. We conclude that the APR has validity as a physiologic parameter which localized regional excessive residual volume and correlates well with RV/TLC, the "gold standard" pulmonary function index of obstructive airway disease.

Scintigraphic evaluation of liver transplant function.

Since the initiation of liver transplantation at our institution 9 yr ago, 73 patients ranging in age from 8 mo to 64 yr have undergone this procedure. In the immediate postoperative period and at various times thereafter as deemed necessary, radionuclide studies were performed using one of the iminodiacetic acid (IDA) derivatives labeled with 99mTc. Initially, these studies were performed using labeled PIPIDA with a shift to diisopropyl IDA when this latter agent became available. The IDA agent is administered as a bolus so that the "flow" and "pooling" may be viewed immediately after injection. This is followed by sequential imaging at various times up to 24 hr, with optional graphic tracings of hepatic and bowel patterns of uptake and clearance of radioactivity. An analysis of the initial portion of the IDA scan yields useful information regarding the arterial and portal venous supply of the liver. The rapidity of hepatic concentration and excretion provides a direct measure of hepatocyte function which is particularly helpful when used sequentially to follow the response of the liver to therapy for rejection or infection. The study is also used to assess the biliary system for obstruction or leaks.

Airflow measurement inaccuracies in aerosol imaging.

Aerosol production using inclined compressed air tanks may be subject to error caused by airflow meter variability and by the degree of inclination of the air-flow meter. Since most of these tanks are used in an inclined position, it is important for clinicians to be aware of these errors.

The preliminary evaluation of Mn DTPA as a potential contrast agent for nuclear magnetic resonance imaging.

The pharmacokinetics of 54Mn administered as Mn-diethylenetriamine pentaacetic acid (DTPA) are being investigated to determine if tissue-specific uptake of manganese could be observed while increasing urinary excretion. This chelation and increased excretion should reduce toxicity. In order to obviate the need for repetitive quantitative nuclear magnetic resonance imaging (NMR) we have substituted tracer amounts of a radioisotope of manganese, Mn-54, for the stable ion. By 6 hours, 58 +/- 7% of the injected dose had been excreted in the urine. Peak liver accumulation occurred within 30 minutes (0.50 +/- 0.14% injected dose/g X kg body weight). The pancreas also showed a relatively high accumulation of tracer (0.25 +/- 0.04%/g X kg body weight), reaching a peak at 4 hours. The pancreas to liver ratios were highest at 6 hours (0.7). There was also a substantial accumulation of the manganese in bile. The blood concentration fell very rapidly with little tracer remaining in the blood at 1 hour. Based on these pharmacokinetics, imaging experiments were conducted before, immediately after, and 9 or 24 hours postinjection. These images showed enhanced kidneys and, later (at 9 hours), an excellent parenchymal-collecting system differentiation. The gallbladder was negatively enhanced. The liver showed either increased or decreased signal strength relative to skeletal muscle depending on the pulse sequence used. We conclude that Mn++, administered as Mn-DTPA, merits further investigation as an NMR contrast agent.

Clinical use of indium-111 labeled blood products.

Following the introduction of In-111 oxine as a label for blood cells by McAffee and Thakur in 1976, these procedures have become increasingly important in the practice of nuclear medicine. Of particular interest are studies involving the use of labeled leukocytes for the detection of focal infection. The clinical utility of labeled platelets is less well developed, although the use of platelets to detect the formation of thrombi in blood vessels and on vascular grafts and prostheses is gaining prominence. This report summarizes the techniques presently employed at the University of Minnesota for the labeling of blood products, and their clinical use. Consideration also is given to the desired expertise and cost factors involved in the labeling of leukocytes and platelets.