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Background: The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required., Methods: A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC. 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). 99(m)Tc (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity., Results: High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity., Conclusions: High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion.

A small abut important subset of patients with differentiated thyroid cancer will die of disease. Our approach to therapy treats almost all patients similarly, with aggressive surgery and I-131 therapy. Meticulous follow-up should include multiple I-131 diagnostic scans using at least 5 to 10 mCi of I-131 with attention to proper patient preparation and good quality procedures. Thyroglobulin levels should be monitored, and other radiographic diagnostic procedures, including thallium scans and MR imaging, should be used as needed. Until screening tests are discovered which will accurately pinpoint patients at high risk for aggressive, recurrent thyroid cancer, the best course of action appears to be aggressive management, including radioiodine therapy.

Granulocyte transfusions are associated with a number of side effects including febrile transfusion reactions and occasionally pulmonary infiltrates. There is evidence that the presence of preformed antibodies may be a cause of these complications. In this study, allogeneic 111Indium-labeled granulocytes were used to evaluate the pulmonary retention of radioactivity in alloimmunized and non-alloimmunized patients in an attempt to assess antibody effect on granulocyte migration. After injection of labeled allogeneic granulocytes into neutropenic patients, the ratios of lung to heart activity were calculated for the first 30 min of scanning. There was significantly greater retention of radioactivity from cells in the lungs of patients who were alloimmunized, having both lymphocytotoxic (anti-HLA) and leuko-agglutinating antibodies, compared to the activity in the lungs of non-alloimmunized patients (P less than .001) or of patients receiving autologous granulocytes (P less than .001). This study demonstrates that labeled, mismatched granulocytes may be retained in the lungs for a significantly longer time in patients with preformed antibodies. This implies that transfusion of large numbers of such mismatched granulocytes, i.e., granulocyte transfusions, may also be retained in the lungs of alloimmunized patients, which could lead to pulmonary compromise. Therefore, granulocyte transfusions from random donors should not be given to alloimmunized patients.

The relationship between a history of Kaposi's sarcoma (KS) and serum titers to cytomegalovirus (CMV) among homosexual patients with acquired immunodeficiency syndrome (AIDS) was studied. Individuals with a history of AIDS and biopsy-proven or clinically confirmed KS were identified and compared with AIDS patients who did not have a history of KS. By demographic parameters and level of immunosuppression, the two groups were similar. Titers to CMV among the 53 AIDS patients (using an indirect fluorescent antibody [IFA] system) demonstrated a median titer for the first group of 1:512 and 1:2048 for the second. The two groups, however, did not differ in a matched study using a McNemar's test for correlated proportions. Wilcoxon ranked sum test performed on the data also demonstrated that the two groups did not differ with respect to the distribution of CMV titers. Serologic data failed to demonstrate a role for CMV infection in the pathogenesis of KS.

Atresia and hypoplasia of the bile ducts are the most common congenital biliary anomalies of clinical importance. Surgical correction can help about 10% of these infants. However, surgery should be performed within the first month of life to avoid irreversible liver parenchymal changes. It is difficult to separate the surgical condition, biliary atresia, from conditions in which the trauma of laparotomy should be avoided, such as neonatal hepatitis and other clinically indistinguishable causes of obstructive jaundice. Radionuclide imaging with the 99mTc-labeled N-substituted iminodiacetic acids (HIDA, PIDIDA, DISIDA, etc) have been helpful in the differential diagnosis of biliary atresia.

Mice bearing transplanted glioma received 0.9% NaCl, 0.1 mg of BLM, or 200-250 microCi of 111In-BLM (0.1 mg BLM) daily for 5 days intraperitoneally. After therapy, tumor sizes were in the order NaCl greater than BLM greater than 111In-BLM. On the 11th day after the first injection, tumor size (mm3) in the 111In-BLM group was 1,220; in the BLM group, it was 2,310 (P less than .025). After intratumor injection of a total dose of 0.1 mg of BLM/gm tumor weight, or of 1 mCi/gm tumor weight of 111In-BLM (carried by 0.1 mg of BLM/gm tumor weight), the tumor size decreased in the 111In-BLM group more than in the BLM group. On the 5th day after the 2nd dose therapy, the tumor size in the 111In-BLM group was 2,020; in the BLM group it was 4,220 (P less than .05). Host weights for these two groups were similar. The necrotic area in the tumor was much greater in the 111In-BLM group than in the BLM group. These results suggest the use for radiotherapy and chemotherapy.

Gallium 67 scanning is an effective method of detecting inflammatory lesions, especially abscesses. A 10-year-old boy with aplastic anemia and severe leukopenia and granulocytopenia had a psoas abscess diagnosed by gallium scan. The patient died with Candida spesis 18 days after bone marrow transplantation. At autopsy, a chronic psoas abscess with Candida was found. The gallium scan offers a clinically effective and noninvasive means of evaluating suspected infection in the granulocytopenic patient.

A rational, multidisciplinary approach to Hodgkin's disease and the non-Hodgkin's lymphomas has been responsible for major advances in therapy. Invasive diagnostic procedures and exploratory laparotomy, with their associated complications, make nontraumatic radionuclide imaging most appealing in both the clinical staging of disease and in evaluating therapy. Gallium-67-citrate, the tumor scanning agent of the early 1970's, has demonstrated a marked affinity for Hodgkin's disease and the other lymphomas. False positives are few, with sensitivity greater than 70% throughout the spectrum of Hodgkin's disease and the histiocytic lymphomas. In addition to confirming sites of suspected neoplasm, this agent has proved useful in the detection of occult involvement. Moreover, resolution of abnormal gallium-67 concentrations on follow-up studies functions as a visual ancillary index of therapeutic response. The value of wholebody gallium-67 scintigraphy is further enhanced when used in conjunction with routine technetium brain, bone, liver, and spleen scans. While the diagnostic accuracy of gallium-67 studies has been limited in the abdomen due to bowel activity, our attempts to improve these results with the tumor-seeking radiopharmaceutical indium-111-Bleomycin were unrewarding and subsequently were discontinued. Finally, radionuclide lymphography has also been explored. Its diagnostic usefulness in detecting pelvic and abdominal lymph node involvement warrants further investigation.

A procedure is described that generates a series of images spanning an average respiratory cycle. Images are constructed from scintigraphic data with similar respiratory flow and volume characteristics so that they may be displayed in continuous-loop movie format. This technique is noninvasive and requires little patient cooperation or technologist time. It should be most useful in investigations of dynamic pulmonary function, but may be applied to any radionuclide study affected by respiratory motion.

The potentially fatal interstitial pneumonia of Pneumocystis carinii is a frequent opportunistic invader of patients treated for malignancy with immunosuppressive and cytotoxic agents. Generalized Ga-67 pulmonary localization which is markedly disproportionate to the clinical and radiographic findings has led to earlier diagnoses by open lung biopsy in this setting. The potential usefulness of gallium scintigraphy in patients with suspected P. Carini pneumonia is presented.

The tissue distributions in glioma-bearing mice given injections of [111In]bleomycin (BLM) indicated that tumor concentrations and ratios of tumor to blood, muscle and brain for [111In]BLM-B2 and -A2 were higher than those for unfractionated [111In]BLM. Autoradiographs of electrophoretic gels of urine containing [111In]BLM or one of its fractions differed from those containing 111InCl3. [111In]BLM and its fractions (A2 and B2) were found to be stable in vivo. The fractions may be more useful in the clinic than [111In]BLM.

Ten weeks after the birth of her first child by Caesarian section, a 27-year-old woman was admitted for evaluation of a possible central nervous system lesion. Four hours after i.v. administration of 15 mCi of Tc-99m for a brain scan, the patient breast-fed her infant; then became concerned about the possibility of radioactivity in her breast milk. Total body gamma-ray measurements of the infant indicated ingestion of 82.5 muCi Tc-99m (corrected for effective T 1/2), while ingestion calculated from gamma-ray measurements of serial milk samples was 75.6 muCi. The single organ radiation dose for the thyroid as the critical organ was 300 mRad, whereas that to the total body was 12 mRad (values derived from 82.5 muCi determined by whole body counting). Had breast feeding been continued at 4-hr intervals, the total ingested activity would have been 94.8 muCi giving the infant a dose of 380 mRad to the thyroid and 16 mRad to the whole body. Had the feeding been given 1/2-hr after injection 726 muCi would have been ingested, increasing the dose by a factor of 10.

Abdominal retractors that are fixed to the operating table provide an electrical pathway to earth and are unsafe. Modifications to ensure the electrical safety of two table mounted abdominal retractors by the incorporation of insulators are described. Results of electrical testing show that the insulators provide high levels of insulation to direct current, 50 Hz alternating current and 400 kHz radio frequency current.

Hepatic hydrothorax is a complication in approximately 5% of patients with cirrhosis. Ascites is almost always present and helps to suggest the correct diagnosis. However, when ascites is absent, radionuclide imaging has proven to be helpful in establishing that the pleural effusion originated from ascitic fluid. When pleural fluid is rapidly removed, such as by thoracostomy tube drainage, the radioisotope may accumulate outside the thorax and produce a negative scan of the chest. When the radionuclide scan is nondiagnostic and the pleural space is being rapidly drained, the pleural fluid collecting system should always be imaged before rejecting a diagnosis of hepatic hydrothorax.

Premature fusion of the sutures of the skull has been extensively analyzed and several diagnostic imaging modalities have been proposed. Radiographic, scintigraphic and computed tomographic features of craniosynostosis have been reported. This study was initiated (a) to determine the value and accuracy of plain skull radiography, skull scintigraphy and cranial CT; and (b) to determine the optimal imaging modality for the evaluation of a clinically suspected craniosynostosis. The study is based on 36 patients with clinical suspicion of craniosynostosis who underwent craniectomy and cranioplasty. One hundred and three sutures were pathologically and/or surgically evaluated. The overall accuracy rate for skull radiography was 89%, skull scintigraphy, 66%, and cranial CT, 94%. Routine skull series are adequate in the majority of cases of craniosynostosis. Skull scintigraphy is less accurate, more costly, and has a limited role in the evaluation of craniosynostosis. Cranial CT should be reserved for those cases in which the findings in the routine skull series are not clearly positive or negative, or in cases of more complex craniofacial anomalies.

The role of the hospital biomedical engineer is described with reference to design and development of equipment and its maintenance, provision of a technical advisory service, and teaching.

This study analyzes the value of the liver scan as a preoperative screening procedure for occult liver metastases in patients with melanoma, sarcoma, head and neck carcinoma, and pelvic carcinoma. The records of 566 consecutive patients admitted to the Surgery Branch of the National Cancer Institute between 1969 and 1974 were reviewed and 323 patients were found acceptable for inclusion in the study. In these patients, although the liver scan had an overall accuracy of 95%, the scan identified only 50% of the patients with occult metastases to the liver and did not siginificantly add to the yield of the other screening procedures. It was useful as an adjuvant to an abnormal routine workup to confirm and localize metastases to the liver. Scans with only non specific abnormalities were of little help. Liver metastases were not identified in any patients with sarcoma, head and neck cancer, or clinically localized carcinoma of the cervix. Therefore, the liver scan was determimed to be an unnecessary part of their screening workup. Patients with recurrent or advanced carcinoma of the cervix and advanced melanoma were found to have an increased incidence of liver metastases. There was a 10% incidence of occult metastases to liver in patients with melanoma and the incidence increased with advancing clinical stage of disease. Even in this high-risk group of patients the screening liver scan did not significantly add information to that gained by history, physical examination, and blood work.

In a recently developed, two-compartment liquid scintillation vial, the evolution of 14CO2 resulting from bacterial metabolism of uniformly labeled d-glucose was measured sensitively, cumulatively, and automatically in a liquid-scintillation counter. In each of eight species tested, a period of log-linear expansion of cumulative counting rate with time was observed. The exponential increase in cumulative counting rate was related to cell replication time by the integral of a first-order differential equation. Within a given species, the replication time measured by radioassay was found to be remarkably constant, unaffected by a fourfold variation in the activity of added labeled d-glucose, insensitive to the presence of carrier dextrose, and independent of the number of bacteria in the initial inoculum over a range of five orders of magnitude. These experiments demonstrate that the replication rate of an organism in culture is a highly reproducible characteristic that is susceptible to precise radiometric measurement in fundamental units of time under a variety of experimental conditions.

A man with an enlarged and tender left calf, chest pain, intermittant hemoptysis, and shortness of breath was referred for a lung scan. Positioning for the ventilation part of the study revealed a high level of radioactivity in the lungs, kidneys, bladder, colon, and salivary glands. The patient denied previous hospital studies and suggested that he may have become contaminated while transporting radioactive materials as an independent truck driver. He was found to be a classic example of Munchausen's syndrome.

111Indium-bleomycin (111In-BLM) and 57Co-bleomycin (57Co-BLM) were prepared and their distributions were compared in the tissues, blood, and urine in tumor-bearing and in untreated mice and rats. Autoradiographs of electrophoresis gels showed that patterns for urine from untreated and tumor-bearing animals, collected 1-3 h or 48 h after injection of 111In-BLM were similar to those for in vitro mixtures of urine and 111In-BLM, but differed from the patterns obtained with 111InCl3 under in vivo or in vitro conditions. In rats bearing mammary adenocarcinoma, 48 h after administration of the radiopharmaceutical, the activity ratio of tumor to eleven different tissues was 1.2-4.6 times higher for injected 111In-BLM than for 111InCl3 (P less than or equal to 0.001 or P less than or equal to 0.05). Imaging with a gamma camera depicted tumors in mice more distinctly with 111In-BLM than with 111InCl3. These findings were interpreted as reflecting the stability of 111In-BLM in vivo. The tumor concentration (%dose/g) was higher for the viable area than for the necrotic area for 111In-BLM, but the reverse was true for 57Co-BLM.

In patients with aortic regurgitation,, left ventricular dysfunction at rest, which is associated with a poor long-term prognosis, often develops before severe symptoms. To determine whether evidence of left ventricular dysfunction could be detected before it appeared at rest, 43 patients with severe aortic regurgitation were studied using radionuclide cineangiography during exercise. In 30 normal subjects, left ventricular ejection fraction increased during exercise (57 +/- 1 percent [mean +/- standard error] at rest, 71 +/- 2 percent during exercise, P less than 0.001). In contrast, among 21 symptomatic patients, ejection fraction was normal at rest in 14 patients (average 47 +/- 2 percent) but normal during exercise in only one patient (average 38 +/- 2 percent, P less than 0.001). Ejection fraction was normal at rest in 21 of 22 asymptomatic patients (average 62 +/- 2 percent) but was normal during exercise in only 13 (average 57 +/- 3 percent, P less than 0.001). Thus, exericse-induced left ventricular dysfunction can precede symptoms and dysfunction at rest. Radionuclide assessment of left ventricular function during exercise may prove valuable in sequentially following the state of left ventricular function in patients before the onset of symptoms or of irreversible left ventricular failure.

By providing information on two parameters, dual-energy computed tomography can offer clinically useful tissue signatures for metallic deposits (Ca) or injected iodine, as well as for different normal and abnormal types of brain parenchymal tissues and CSF. Cerebral CT was performed on 36 patients and tissue differences analyzed using Hounsfield notation.

Positron emission tomography was used to measure local cerebral glucose utilization by the 1-[18F]fluoro-2-deoxy-D-glucose technique in 23 patients with cerebral gliomas. All 10 high-grade (III and IV) astrocytomas demonstrated a region of high activity with a glucose consumption of 7.4 +/- 3.5 (SD) mg/100 gm per minute. The 13 low-grade (I and II) gliomas had a glucose metabolic rate of 4.0 +/- 1.8 mg/100 gm per minute, with no distinctly visible hot spot. Thus, we found a correlation between rate of glycolysis and malignancy in primary cerebral tumors. Cerebral cortical glucose utilization was often depressed in areas adjacent to or neurally connected to the tumor site, and there was focal irregular delta wave EEG activity in these areas.

A retrospective study to determine the value of bone and brain scans was performed in preoperative patients with melanoma, sarcoma, cancer of the head and neck and carcinoma of the pelvis. No occult metastases were identified in 170 patients in whom brain scan was performed. On late follow-up data, eight patients had neurologic symptoms develop and had brain metastases identified on scan. Of 223 bone scans performed, only one distant metastatic lesion was identified. It is, therefore, suggested that, in these types of patients, bone and brain scans be reserved for those with symptoms referable to the neurologic or skeletal systems.

Renal localization of 67Ga citrate has been observed in 1.7% of 2,000 whole-body gallium scans in three major diseases: lymphoreticular neoplasms, leukemia, and malignant melanoma. Correlation of this finding with autopsy data in 13 cases revealed 9 with tumor and 2 with an inflammatory process. Findings in two cases were normal. In the remaining patients, correlation with abnormal urograms and laboratory data was poor. Nevertheless, gallium localization in the kidneys may be the first indicator of renal involvement with either tumor or inflammation.

The clinical and laboratory diagnosis of acute acalculous cholecystitis is difficult, and the reliability of various diagnostic imaging techniques has not been established. The results of several imaging procedures performed over a 6-year period on 56 patients with clinically suspected acute acalculous cholecystitis were evaluated retrospectively. Sonography and CT were both highly sensitive (92% and 100%, respectively) and specific (96% and 100%, respectively). Hepatobiliary scintigraphy was compromised by frequent false-positives; the result was a specificity of only 38%. Percutaneous bile aspiration was insufficiently sensitive (33%) for diagnosis. Sonography was as sensitive as hepatobiliary scintigraphy and was more specific in establishing the diagnosis. Because sonography is relatively inexpensive and can be performed at the bedside, it should be regarded as a satisfactory screening procedure. However, CT is a good alternative in an easily transported patient when other intraabdominal disease is suspected.

A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy.

Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption.

Sixty-one total body I-131 scans performed on 29 patients who were post-thyroidectomy for differentiated thyroid cancer were retrospectively reviewed to determine the frequency of hepatic visualization. The liver was seen in 52% of the patients. Diffuse liver uptake was present on 5 of 38 (13%) diagnostic (10 mCi) scans and on 12 of 23 (52%) post-therapy (80-150 mCi) scans. None of these patients showed clinical or laboratory evidence of hepatic metastases during a mean follow-up period of 18 months. We conclude that physiological diffuse liver activity is seen frequently on I-131 total-body scans.

Abnormalities of right and left ventricular ejection fraction and segmental wall motion may be detected by radionuclide angiography (RNA) following blunt chest trauma. Of 111 patients with blunt chest trauma who were admitted to a large regional shock trauma center and underwent combined first-pass and equilibrium gated RNA, abnormalities were present in 40 (36%). These abnormalities were confined to the right ventricle in 33 patients. There was a positive association between RNA abnormalities and the presence of right bundle branch block (10 of 40, p less than 0.05) and a negative association between RNA abnormalities and the finding of rib fractures (6 of 40, p less than 0.05). The in-hospital death rate of these patients was low (3 of 40 patients with an abnormal RNA and 2 of 71 patients with a normal RNA). Follow-up RNA was performed at 10 +/- 4 days in 26 of the 40 patients with initially abnormal scans, and 22 (85%) of the 26 had reverted to normal. Thus although RNA abnormalities appear common following blunt chest trauma, among patients who survive for more than 24 hours and who undergo subsequent RNA, the complication rate is low despite an abnormal scan. We conclude that routine RNA adds little to clinical management following acute blunt chest trauma.

The authors studied 54 patients with multisystem trauma, including blunt chest injury, using combined dynamic first-pass and electrocardiographically (ECG) gated radionuclide ventriculography (RNV) to evaluate for posttraumatic myocardial dysfunction. Twenty-six of 54 (48%) patients had abnormalities of ventricular wall motion. The ventricular dysfunction was confined to the right ventricle in 92% of cases. In general, abnormalities consisted of right ventricular dilatation and diffuse hypokinesia, although in seven cases there were localized wall-motion abnormalities. The right ventricular ejection fraction of those patients with wall-motion abnormalities was significantly lower than those with normal studies. Left ventricular ejection fraction did not differ significantly between these groups. ECG changes were not associated with the cardiac dysfunction demonstrated scintigraphically, nor was there a relationship between the number or type of extrathoracic or thoracic injuries demonstrated by RNV. Follow-up studies obtained in 15 cases showed a significant overall improvement in cardiac function by 3 weeks after injury. Combined first-pass and ECG-gated RNV is useful for the identification and follow-up of patients with posttraumatic cardiac dysfunction.

The sacral tubercle, S1 posterior spinous process, can appear as intense as the sacroiliac joints on posterior bone scan in 4% of normal adult male patients. Due to sexual differences in anatomy, the scan appearance of the sacrum can cause false-positive readings. The converse, false-negative readings, can occur if the sacral intensity is taken as a constant when comparing ratios of sacroiliac joint intensities and sacral intensities on bone scans of patients with sacroiliac disease. This study demonstrates the normal anatomy of the sacrum and presents a sequence of tests to diagnose disease in the sacrum.

Whole-body gallium imaging was evaluated as a diagnostic tool for 14 patients with Burkitt's lymphoma, and a dramatic gallium affinity for the tumor was demonstrated. The gallium image is recommended as a staging procedure and as an effective test for determining the therapeutic response.