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Current methods of assessing cerebral blood flow (CBF) are limited in their ability to provide data at the bedside in a timely, inexpensive, and continuous fashion. Since the palpebral conjunctiva is perfused by branches of the internal carotid artery, perfusion of this tissue may reflect global CBF. Conjunctival oxygen tension (PcjO2), PaO2, PaCO2, and pH were measured in ten healthy subjects during normal ventilation and active hyperventilation. CBF was measured simultaneously using positron emission tomography. CBF decreased from an average of 64.3 +/- 15.1 ml x 100 g-1 x min-1 during baseline measurements to 33.2 +/- 8.4 ml x 100 g-1 x min-1 during hyperventilation. The ratio of PcjO2 to PaO2 (the PcjO2/PaO2 index) decreased from 0.53 +/- 0.07 to 0.35 +/- 0.09 in the same time period. The PcjO2/PaO2 index was significantly correlated with CBF (r = .78, p less than .001). We conclude that the PcjO2/PaO2 index may reflect the reduction in CBF induced by hyperventilation in normal humans, and should be investigated further as a method of assessing CBF in other settings which can result in globally reduced cerebral perfusion.

The basic principles underlying nuclear magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) are explained. Examples of work relating to tumor metabolism are given and some of the important findings of clinical interest are presented. The future prospects of both systems are explored.

The biodistribution of 3F8, and IgG3 murine monoclonal antibody (MoAb) specific for the disialoganglioside GD2, was studied in nude mice xenografted with human neuroblastoma (NB). 3F8 conjugated to radioactive iodine and injected intravenously localized selectively to seven human NB when compared with Ewing's sarcoma and Hela cell xenograft controls. Uptake in NB was shown to be specific for MoAb 3F8 when contrasted with pooled mouse IgG or irrelevant IgG3 MoAb controls. Both small (50 mg) and large tumors greater than 2 g) showed radiolocalization. The percent injected dose uptake per gram tumor ranged from 8 to 50% and was inversely correlated with tumor size. Optimal tumor to normal tissue ratios were reached by 24-48 hr. There was no abnormal uptake in the reticuloendothelial system and the MoAb did not cross the blood-brain barrier. Based on the kinetics of the amount of radioactivity deposited in tissues, the relative radiation dose to normal organs was estimated to be 1% to 20% of the tumor dose. The MoAb 3F8 is useful for targeting radioactivity to human NB in vivo and the nude mice xenograft model may allow optimization of parameters that influence such biodistribution.

A safe, sensitive and convenient technique using 131-I fibrinogen for detecting deep venous thrombosis in postoperative patients has been developed. A total of 47 volunteers over age 40 years about to undergo major operation were studied prospectively. Neither in 20 patients given heparin as part of the surgical procedure or for prevention of superficial phlebitis in the arm during intravenous therapy nor in the 27 others not given anticoagulants before, during or after operations was there evidence of venous thrombosis in the leg or pulmonary embolism either by the 131-I fibrinogen scan nor by clinical course. A retrospective review of hospital records confirmed the relative rarity of pulmonary embolism as a cause of identified morbidity and mortality in surgical patients. Of 54, 183 adult patients discharged from the University Hospitals of Cleveland during 1972 and 1973, 197, or 0.4 per cent, were diagnosed as having pulmonary embolism, and of these only 32, or 16 per cent, occurred in postoperative surgical patients. A review of the autopsy records of the same institution for the same time also revealed a low incidence of deaths due to pulmonary embolism among the surgical population, only 180, or 0.8 per cent, of the 22, 449 adult surgical admissions. Although feasible to perform, the value of the radiofibrinogen method of detecting deep venous thrombosis in postoperative patients as a routine measure is questioned.

The authors report a rare complication of nuclear bone imaging, iodide mumps, and describe its appearance on the subsequent radionuclide salivary gland study.

Several antineuroblastoma monoclonal antibodies (MoAbs) have been described and two have been used in radioimmunoimaging and radioimmunotherapy in patients. MoAb 3F8 is a murine IgG3 antibody specific for the ganglioside GD2. Radioiodine-labeled 3F8 has been shown to specifically target human neuroblastoma in patients, and radioimmunoimaging with this agent has provided consistently high uptakes with tumor-to-background ratios of greater than or equal to 10:1. Radioimmunotherapy has been attempted with both MoAb 3F8 and MoAb UJ13A, and although encouraging results have been obtained, dosimetry data and tissue dose response information for these agents is lacking, which impedes the development of such therapy. 124I, a positron emitter, can be used with 3F8 in positron emission tomography (PET) scanning to provide dosimetry information for radioimmunotherapy. The tumor radiation dose response from radiolabeled MoAb also can be followed with PET images with fluorodeoxyglucose (FDG) scanning of neuroblastoma tumors. Results to date indicate that radioimmunoimaging has clinical use in the diagnosis of neuroblastoma and the potential for radioimmunotherapy for this cancer remains high.

In a previous study, the authors showed that iodine-131 labeled monoclonal antibody (Mab 3F8) could be used to image human neuroblastoma xenografts in mice with excellent tumor-to-tissue ratios. In this study they report their experience with six patients scanned with radiolabeled 3F8. There was strong accumulation of the labeled antibody in viable tumor, but no significant uptake was noted in normal brain, liver, spleen, or adrenal glands. Tumor-to-nontumor activity ratios varied but were approximately 10:1-20:1. This ratio yields good contrast for visualization. Time-activity curves show that radioactivity levels in normal tissue have a half-time of about 40 hours, whereas tumor tissues show a half-time of about 60 hours. Significant gastric secretion of free iodine demonstrated that the Mab was being deiodinated. Calculated radiation doses indicate that tumors receive at least ten times the dose to other tissues. The results indicate that Mab 3F8 has clinical potential for both imaging and therapy of human neuroblastomas.

A phantom was designed to test computed tomography (CT) scanner performance relative to spatial resolution, contrast resolution, field uniformity, spatial linearity, artifact resistance, and radiation dose. Translate/rotate, stationary detector with rotating x-ray tube, and rotate-only scanners were tested under conditions that produced the best possible results for each machine within the dose ranges used in clinical practice. Machines can be ranked according to results for each parameters tested. The range of performance exhibited on machines tested was unrelated to class of scanner. Further, machine dedication to a particular body region did not necessarily secure superior results for that region. Spatial resolution at low contrast levels (poor on most machines) seems to be the most sensitive test of performance.

Magnetic resonance imaging (MRI) was compared with iodine-131-labeled monoclonal antibody scanning for ability to detect bone marrow metastases in the spine, pelvis, and femurs of children with disseminated neuroblastoma. The five patients in this study had received high-dose chemotherapy and radiation, either with (N = 2) or without (N = 3) bone marrow transplants. MRI disclosed marrow abnormalities at all sites detected with the radiolabeled antibody, which is highly specific for neuroblastoma. However, several diffuse and multifocal marrow changes apparent on MR scans were not present on scintigrams, indicating that MRI is probably less specific than monoclonal antibody imaging. Both methods were more useful than conventional radiography, computed tomography, and 99mTc-MDP bone scans for identifying sites of marrow involvement by neuroblastoma.

The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I-radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities.

The effect of different mAs settings on computed tomobraphy (CT) image quality was evaluated by a clinical study and phantom studies. In the clinical portion of this study, a number of CT images, obtained at various mAs settings, were reviewed by experienced CT interpreters. From these same images, graphs were charted of the root-mean-standard deviation (RMSD) vs. body size; there appeared to be a linear relationship between noise, as measured by RMSD, and body size. A performance phantom was used to evaluate the effect of the different mAs settings on resolution. There was some loss in low contrast resolution at 6 and 20 mAs; however, the resolution was identical at 40 and 100 mAs.