5-125I-iododeoxyuridine as prototype for radionuclide therapy with Auger emitters.
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Biomedical subjects
Publications and source records attributed to S J Adelstein.
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The feasibility of a new method for in vivo regional bone calcium measurement has been studied in phantoms using the 160 MeV Harvard cyclotron, Advantages include the capability of measuring bone calcium directly directly in a well defined anatomical region (such as one or several vertebrae) and restriction of the dose to the immediate region of interest. Proton activation of 40Ca (97% natural abundance) produces radionuclide 38K. Its 2-17 MeV gamma ray (T 1/2 = 7-71 min) is detected by a NaI counter. Separation of this activity from room background and interfering nuclides, 14O and 34Clm, proceeds by decay curve analysis. Phantom studies showed the dependence of 38K activity to be highly linear with calcium content (r= 0-998). Non-linearities with dose did not appear below the 20 rad level. The precision of measurements on a phantom with two calf vertebrae exposed to 2-4 rad was 3% and was mostly limited by counting statistics. System reproducibility on phantoms given a high dose proved better than 0-5%.
The usefulness of performing diagnostic staging tests on patients thought to have operable bronchial carcinoma was explored by modeling the diagnostic and therapeutic processes for patients with this disease. The availability of appropriate autopsy and survival data allowed this investigation. We analyzed the results of two diagnostic and therapeeutic strategies: a test strategy in which extensive staging tests are performed preoperatively on patients with Stage I or II disease and a no test strategy in which such examinations are not performed. Average survival times are little affected by the choice of the test or no test diagnostic strategy. The chance of an immediate postoperative death, of an unnecessary operation and of a long term cure are affected more. Within the error of measurement, financial costs for the two strategies are probably the same. This investigation is a prototype for estimating the value of diagnostic staging tests and the effects of consequent alternative methods of treatment for patients with known malignant conditions.
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Progress in the development of cardiovascular nuclear medicine can be accelerated by close cooperation between cardiologists and nuclear medicine physicians in the planning, performance and interpretation of diagnostic tracer studies. The special needs of patients with acute cardiovascular disorders often require supplementation of the hospital's central nuclear medical facility with one or more satellite units in or near the coronary care unit, cardiac operating suite, postoperative intensive care unit or emergency room. Newly emerging noninvasive cardiac diagnostic laboratories should be equipped to perform certain nuclear medicine procedures. Selected nuclear diagnostic procedures also can provide useful supplemental information during cardiac catheterization and angiography.
Tumor-seeking radiopharmaceuticals have been employed in the diagnosis of primary neoplasms, in the detection of distant disease, particularly in the localization of tumor foci to facilitate biopsies and the planning of radiation portals, and in assessing the response to tumor therapy. At the present, there is no ideal tumor-scanning agent. However, several approaches appear to be useful and offer promise for further study. The greatest experience has been with Gallium-67, which has major utility in the staging of Hodgkin's disease, in the diagnosis of bronchogenic carcinoma, in the detection of certain metastatic brain tumors, in the identification of recurrent disease, and in the noninvasive diagnosis of leukemic complications. A number of radiolabeled antibiotic and chemotherapeutic agents have shown promise, including tetracycline and bleomycin. A major drawback, however, of these agents which is shared with Gallium-67 is that they appear to be sequestered by inflammatory as well as neoplastic tissue. A most intriguing approach is the use of radiolabeled antibodies to tumor-associated antigens. Animal and clinical experiments have employed antifibrin, antifibrinogen, anticarcinoembryonic antigen, and antiferritin. Theoretically, agents such as these should allow for greater tumor specificity.
Ribonuclease was irradiated under conditions such that ethanol radicals were the main reactive species in solution. Sephadex gel filtration of the irradiated solution demonstrated that ethanol radicals had reacted with the ribonuclease and had become firmly bound to the enzyme molecule. The number of ethanol molecules bound to ribonuclease was a function of dose and correlated with the loss of enzymatic activity and with the changes in the molecular configuration of the enzyme molecule.
The usefulness of various modalities in evaluating pleuritic pain in young patients and in isolating cases of pulmonary embolism was assessed using likelihood ratios and the receiver operating characteristic (ROC) curve. History and physical, laboratory, and radiographic finding were used disjunctively to establish an ROC curve. The percentage of patients found to have pulmonary embolism increased monotonically with certain critical pieces of diagnostic data. For example, a history and physical examination alone detected 80% of patients with pulmonary embolism; a chest radiograph raised the percentage to 95%; and the addition of a lung scan increased the percentage to 100%. Thus, with proper interpretation of clinical and radiographic data, the lung scan has only a marginal impact upon the sensitivity with which pulmonary embolism is detected. Its major value is an increased specificity in the diagnosis of pulmonary embolism.
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Bone seeking radiopharmaceuticals were used in conjunction with skeletal imaging techniques to study bone mineral metabolism in beagle jaws. In beagles with chronic destructive periodontal disease, the tooth-supporting bone exhibited an increased uptake of technetium-99m-tin-diphosphonate when compared to control dogs. Scan images of soft tissue and vascular pools in the diseased jaws were normal. When quantitative densitometric data derived from bone scan images were compared, it was found that values reflecting radionuclide uptake in dogs with chronic destructive periodontal disease were six times greater than corresponding values in control dogs.
The value of a diagnostic test lies in its ability to detect patients with disease (its sensitivity) and to exclude patients without disease (its specificity). For tests with binary outcomes, these measures are fixed. For tests with a continuous scale of values, various cutoff points can be selected to adjust the sensitivity and specificity of the test to conform with the physician's goals. Principles of statistical decision theory and information theory suggest technics for objectively determining these cutoff points, depending upon whether the physician is concerned with health costs, with financial costs, or with the information content of the test.
The sensitivity and specificity of the hypertensive intravenous pyelogram and the iodohippuran renogram have been determined for the diagnosis of renovascular disease, and cost-effectiveness calculations have been made for the diagnosis and surgical treatment of patients with renovascular hypertension. When the intravenous pyelogram alone is used to screen representative hypertensive population, 78 per cent of patients with renovascular disease are located, but at the same time an equal number of patients without renovascular diasease have abnormal pyelograms. The renogram, on the other hand, is associated with varying true-positive and false-positive ratios. These data can be plotted in the form of a receiver-operating-characteristic curve. The cost of finding a patient with renovascular disease is about $2,000, and that of a surgical cure is about $20,000. The number of deaths for 100 surgical cures is approximately 15. The dollar cost of screening and treating the total American renovascular hypertensive population is of the order of 10 to 13 billion dollars.
An attempt was made to discover the difference in outcomes between treating all patients with essential and renovascular hypertension by drug therapy independent and ignorant of etiologic classification and identifying the patients with renovascular disease and operating on them. Outcomes were categorized as well without complications of hypertension, alive but suffering from a related morbid illness such as coronary or cerebral arterial disease, and dead from the complications of diagnosis, surgery or high blood pressure. The identification and surgical treatment of hypertensive renovascular disease resulted in an incremental benefit in morbidity over blind antihypertensive medical therapy only when the compliance with medical treatment was about 50 per cent or less (the rate suggested for most patient populations). The study underscores the extent to which the quantitative efficacy of diagnositc and therapeutic procedures depends not only on the inherent risks and benefits but also on related social and medical factors.
Iodine-131-labeled immunospecific gamma globulin derived from immunization of rabbits with F antigen, a tumor associated antogen in Hodgkin's disease, has been utilized for intralymphatic infusion in a patient with known recurrent Hodgkin's disease inthe inguinofemoral and pelvic regions. Rectilinear scanning successfully delineatedthe tumor masses, and external monitoring showed retention of activity in the tumor sitesover an 8-day period.
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The Inter-Society Commission for Heart Disease Resources report concerning optimal resource guidelines for radioactive tracer studies of the heart and circulation is described. This report is an overview of the status of cardiovascular radionuclide diagnostic studies as well as a guideline to the hospital resources (physical and human) required for a high-quality nuclear medicine laboratory dealing with this area of study. These guidelines are directed to physicians and hospital administrators who are currently responsible for planning and organizing nuclear medicine programs or who anticipate a future need for such services in their community.
The status of radioactive tracer studies in cardiovascular diagnosis is summarized. Planning guidelines are suggested for a hospital nuclear medical service including a central nuclear medical facility and satellite units, and resource criteria are given for professional personnel including training and duties, equipment, space, and support system. The administrative organization of a nuclear medical service and case loads are discussed. Guidelines for equipment maintenance and quality controls are described.