Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in patients with malignant melanoma.

The potential usefulness of [C-11]-labeled alpha-aminoisobutyric acid (AIB) for tumor imaging has been demonstrated previously in our findings of increased tumor uptake with C-14-labeled AIB in human melanoma heterotransplants in nude mice, and subsequently, in a single case study using C-11 AIB to demonstrate the extent of metastases in patient with widespread malignant melanoma. We report here on the use of C-11 AIB in ten patients with metastatic or unresectable malignant melanoma. Five patients had intense tracer uptake at all known sites of tumor involvement. A sixth patient had good uptake in metastatic lesions in the shoulder and the pelvis, but did not demonstrate uptake within metastatic lesions in the lungs. Two patients had only minimal uptake over the tumor lesions while the two other patients had essentially normal studies. Further studies with C-11 AIB in patients with melanoma and other tumors are warranted.

Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma.

I-131 metaiodobenzylguanidine (MIBG) imaging was performed in 38 patients with advanced neuroblastoma. Abnormal images were found in patients with elevations of urinary vanillylmandelic acid and dopamine and high serum neuron-specific enolase levels. Normal or minimal elevation of markers was seen in patients with negative images. In follow-up studies after chemotherapy, the disappearance of abnormal uptake was noted in those patients with normal marker values. A persistently abnormal uptake occurred in patients with high marker values. Conversion from a normal image to an abnormal image also occurred in patients whose markers became elevated. I-131 MIBG imaging is sensitive in detecting active foci of a neuroblastoma and is useful in monitoring chemotherapy in these patients.

Perfusion of colorectal hepatic metastases. Relative distribution of flow from the hepatic artery and portal vein.

The importance of portal circulation in the delivery of drugs and nutrients to colorectal hepatic metastases is controversial. Using 13N (nitrogen 13) amino acids and ammonia with dynamic gamma camera imaging, we demonstrate, for the first time in human beings, a quantitative advantage of hepatic artery compared with portal vein infusion. Eleven patients were studied by hepatic artery injection, five patients were studied by portal vein injection, and two patients had injections through both routes. Data collected from the liver for 10 minutes after rapid bolus injection of 13N L-glutamate, L-glutamine, or ammonia were compared with 99mTc (technetium) macroaggregated albumin (MAA) images produced after injection through the hepatic artery or portal vein at the same session. Tumor regions defined from 99mTc sulfur colloid scans were compared with nearby liver areas of similar thickness. For the 13N compounds, the area-normalized count rate at first pass maximum (Qmax) and the tissue extraction efficiency were computed. The tumor/liver Qmax ratios for MAA and 13N compounds were highly correlated. Both tumor and liver extracted more than 70% of the nitrogenous compounds. The tumor/liver Qmax ratios reflect the relative delivery of injected tracer per unit volume of tissue. After hepatic artery injection the Qmax ratio was 1.03 +/- 0.33 (mean +/- SD), significantly exceeding the Qmax ratio of 0.50 +/- 0.34 after portal vein injection (P less than 0.003). Therefore, more than twice as much of a nutrient substrate is delivered per volume of tumor relative to liver by the hepatic artery as by the portal vein; the high extraction efficiency demonstrates that the hepatic artery flow is nutritive; and the delivery of substance in solution (such as nutrients or drugs) to tumor and liver tissue correlates with the distribution of colloids such as macroaggregated albumin after hepatic arterial and portal venous injection.

Abnormal gallium scintigraphy in pulmonary alveolar proteinosis (PAP).

A patient with medulloblastoma of the cerebellum developed dyspnea and hypoxemia. Pulmonary function tests showed decreased lung volume and diffusing capacity, while the chest radiographs initially showed only mild interstitial infiltrates. Repeated gallium scans showed diffuse lung uptake and diagnosis of pulmonary alveolar proteinosis was made by open lung biopsy.

Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB).

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the short-lived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.

Technetium-99m albumin scintigraphy in the diagnosis of protein-losing enteropathy.

While several studies have documented protein losing enteropathy by measuring the excretion of intravenously administered 131I- or 51Cr-labeled albumin, the efficacy of 99mTc-labeled albumin in detecting protein loss in the bowel has not been described. We report here a case of severe protein-losing enteropathy demonstrated by abnormal excretion of 99mTc albumin into the bowel.

Technetium-99m RBC venography revealing bilateral iliac vein obstruction.

Tc-99m RBC venography demonstrated bilateral iliac vein obstruction with subsequent collateral flow through the internal iliac veins into the internal and perimuscular rectal plexuses.

Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma.

A 29 year-old-man presenting with advanced metastatic malignant melanoma was successfully imaged using carbon-11 (11C) labeled alpha-aminoisobutyric acid (AIB), a synthetic, non-metabolized amino acid transported into viable cells by the A-type, or alanine-preferring, amino acid transport system. Tumor located in the hilum of the lung was well visualized with 11C-AIB prior to chemotherapy. A gallium image with liver subtraction using 99mTc-sulfur colloid demonstrated regions of increased activity in liver which correlated with regions of increased activity on the 11C-AIB liver image.

Gallbladder visualization on a technetium-99m MDP bone scan.

A bone scan performed on a 54-year-old woman with metastatic breast carcinoma and concurrent cholelithiasis demonstrated intense gallbladder concentration of radionuclide.

Imaging of human tumors and organs with N-13-labeled L-methionine.

The work described herein is the first reported use of nitrogen-13-labeled L-methionine in human subjects. Three volunteers and 14 patients with a variety of solid tumors were scanned after intravenous administration of L-(N-13) methionine. In both volunteers and cancer patients, uptake of label was seen in the liver and pancreas, with smaller amounts of label detected in the heart, urinary bladder, and salivary glands. Concentration of N-13 in tumor was seen in 12 of the 14 cancer patients. Five had repeat studies after chemotherapy; in each case, the change in tumor uptake of N-13 after N-13 methionine injection paralleled the clinical response to chemotherapy. Three patients had L-(N-13) glutamate scans the same day that they were studied with N-13 methionine. Concentration of the radiolabel in the tumor was very similar for the two compounds in each case. The systemic distribution of N-13 from methionine is similar to that from glutamate, except for a much smaller myocardial uptake and a prominent accumulation in the intestinal region. It is concluded that L-(N-13) methionine is potentially useful as a biologically significant agent for tumor visualization and assessment of therapeutic response.

Radioactive iodine treatment of metastatic thyroid carcinoma with clinical thyrotoxicosis.

We present a case of well-differentiated follicular carcinoma of the thyroid with hyperfunctioning metastases and clinical thyrotoxicosis. The recommended I-131 treatment dose for patients with widespread bone metastases from thyroid carcinoma is 200 mCi. However, in a patient with hyperfunctioning metastatic tumor and increased radioiodine uptake, the treatment dose should be modified. Radiation dosimetry measurements performed on the patient in this study demonstrated that 132 mCi would be a safe therapeutic I-131 dose which would avoid injury to normal radiosensitive tissues. Consequently, she was given a 130-mCi therapeutic dose.

Predicting tumor response in patients with colorectal hepatic metastases.

Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy.

Early detection of anthracycline-induced cardiotoxicity by stress radionuclide cineangiography in conjunction with Fourier amplitude and phase analysis.

Thirty-three cases of anthracycline related cardiotoxicity occurred in our institution in patients with a previously negative cardiovascular history, physical examination, and normal ECG. A total of 95 RNCA studies were performed in this group (73 studies included both rest and exercise RNCA). Twenty-one patients had two or more serial studies. Seventeen had a normal, baseline prechemotherapy study and 16 had studies done following the initiation of therapy. Fourier analysis, consisting of amplitude and phase images, were created for each study. In the subset with a baseline study, the rest LVEF became abnormal first in two of 17 patients (12%), the rest or stress LVEF in ten of 17 (59%), the rest Fourier image analysis in ten of 17 (59%), and the rest or stress Fourier image analysis in 16 of 17 (94%). In the subset without a baseline study, the rest LVEF was abnormal in ten of 16 (63%), the rest or stress LVEF in 15 of 16, (94%), the rest Fourier image analysis in 16 of 16 (100%), and the rest or stress Fourier image analysis in 16 of 16 (100%). The authors conclude that: 1) the exercise RNCA is superior to the rest RNCA alone in the early detection of anthracycline related cardiotoxicity, 2) the single most sensitive indicator of cardiotoxicity is Fourier image analysis; and 3) sequential rest and stress RNCA studies with Fourier amplitude and phase analysis is the most sensitive, noninvasive method of evaluating patients who receive potentially cardiotoxic agents.

Airway humidification with high-frequency jet ventilation.

Humidification of inspired gases is indispensible to prevent serious injury to the tracheal mucosa of patients on mechanical ventilation. High-frequency jet ventilation (HFJV), recently introduced for the management of some forms of respiratory failure, presents unusual technical problems of humidification. The present investigation evaluated a technique to humidify jet gases by delivering small droplets of normal saline in front of the injector cannula, and utilizing the jet flow to nebulize the fluids administered. One millicurie of technetium-99m sulfur colloid (Tc-99m) was diluted in 10 ml of saline and infused in the airway of nine patients supported on HFJV. Six patients were orotracheally intubated and three were tracheostomized. A portable gamma camera was used to determine the distribution of radioactive contrast in the airway every 200 sec. When the injector catheter was directed upward, as was the case in tracheostomized patients, contrast material accumulated in the ventilator lines, and visualization of the airway was limited to the trachea. In orotracheally intubated patients, the injector catheter was generally directed downward, and radioactive contrast material extended beyond the major bronchi. The radioactive tracer reached the most distal airway location in patients with the lowest PaCO2 values. Thus, when humidification systems rely on jet-stream nebulization of fluids, the position of the injector cannula should facilitate saline flow by gravity. In the presence of poor alveolar ventilation, the concomitant risk of inadequate humidification should be considered.

Combined Fourier amplitude and phase imaging in patients with coronary artery disease.

Fourier amplitude and phase image analysis were evaluated in 66 patients. Thirty patients served as a control group and 36 had coronary artery disease (CAD). Each patient in our control group had a rest and exercise radionuclide cineangiogram (RNCA) study (60 total). The amplitude and phase images for controls were uniform. No statistically significant difference in the histogram distribution of amplitude or phase occurred between rest and exercise. Twenty-five patients with CAD had a prior myocardial infarction (MI). Fourier analysis, when compared to the left ventricular ejection fraction (LVEF) and visual cine wall motion analysis, improved the sensitivity of the rest RNCA study to detect CAD from 68% to 92%. Regional Fourier amplitude and phase image analysis demonstrated an 85% sensitivity in localizing regions of previous infarction. Thirteen of 25 patients with prior MI and an additional 11 patients with recent onset of angina but no previous infarction, had exercise RNCA studies. When compared to cardiac catheterization data, regional Fourier amplitude and phase image analysis demonstrated sensitivities of 87% and 80%, respectively, in correctly identifying clinically significant major coronary artery involvement in these two subsets of patients. Fourier amplitude and phase image analysis were also able to distinguish normals from patients with previous MI, and patients with CAD but no prior infarction. All comparisons were statistically significant. We conclude that the semiquantitative image analysis of Fourier amplitude and phase data increases the clinical utility of the RNCA study in patients with CAD.

Fourier amplitude and phase analysis in the clinical evaluation of patients with cardiomyopathy.

Fifty-four patients with a cardiomyopathy were studied by RNCA and Fourier amplitude and phase image analysis. The study group included patients with ischemic cardiomyopathy (27) and an equal number of patients with a primary cardiomyopathy: drug-induced (22), idiopathic (three), radiation-induced (one), and amyloidosis (one). Twenty-eight patients had rest studies alone and 26 had both rest and stress studies (80 total). The mean rest LVEF in the ischemic group was 27.9%, in the drug-induced group 36.5%, and in the idiopathic group 30%. The stress LVEF decreased in 92% of patients with ischemic cardiomyopathy and 45% of patients with primary (drug-induced) cardiomyopathy. Fourier amplitude and phase images were generated for each study. Amplitude and phase images were abnormal in all patients with an ischemic cardiomyopathy. LV amplitude abnormalities were regional and phase was directional. A zone of dysynergy on phase analysis was present in 44% of patients with ischemic cardiomyopathy. In the drug-induced primary cardiomyopathy group, all patients had abnormal amplitude and 86% had abnormal phase. Amplitude abnormalities were global rather than regional and phase patterns were nondirectional. Only one patient had a zone of dysynergy on the phase image. We conclude that the stress LVEF alone cannot consistently differentiate between ischemic and primary cardiomyopathies and that Fourier amplitude and phase analysis may be useful in determining the etiology of a cardiomyopathy (ischemic vs primary).

A clinical evaluation of the RNCA study using Fourier filtering as a preprocessing method.

Forty-one patients (25 male, 16 female) were studied by RNCA in our institution. There were 42 rest studies and 24 stress studies (66 studies total). Sixteen patients were normal, 15 had ASHD, seven had a cardiomyopathy, and three had left-sided valvular regurgitation. Each study was preprocessed using both the standard nine-point smoothing method and Fourier filtering. Amplitude and phase images were also generated. Both preprocessing methods were compared with respect to image quality, border definition, reliability and reproducibility of the LVEF, and cine wall motion interpretation. Image quality and border definition were judged superior by the consensus of two independent observers in 65 of 66 studies (98%) using Fourier filtered data. The LVEF differed between the two processes by greater than .05 in 17 of 66 studies (26%) including five studies in which the LVEF could not be determined using nine-point smoothed data. LV wall motion was normal by both techniques in all control patients by cine analysis. However, cine wall motion analysis using Fourier filtered data demonstrated additional abnormalities in 17 of 25 studies (68%) in the ASHD group, including three uninterpretable studies using nine-point smoothed data. In the cardiomyopathy/valvular heart disease group, ten of 18 studies (56%) had additional wall motion abnormalities using Fourier filtered data (including four uninterpretable studies using nine-point smoothed data). We conclude that Fourier filtering is superior to the nine-point smooth preprocessing method now in general use in terms of image quality, border definition, generation of an LVEF, and cine wall motion analysis. The advent of the array processor makes routine preprocessing by Fourier filtering a feasible technologic advance in the development of the RNCA study.