Outcomes and native renal recovery following simultaneous liver-kidney transplantation.

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver-kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post-SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre-SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20-40 mL/min), although at the most conservative cut-off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post-SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre-SLK renal imaging (OR 3.85, CI 1.22-12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.

Pharmacokinetics of 99mTc(Sn)- and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments in nude mice.

The biodistribution, radioimmunoimaging, and high pressure liquid chromatography activity profiles of 99mTc(Sn) and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments were compared. Nude mice, bearing specific (colon carcinoma, LS174T) and nonspecific (pancreatic carcinoma, MIA) xenografts were given injections of the respective radiolabeled antibody fragments and also of irrelevant 125I-labeled antibody fragments (MOPC-21). The animals were imaged at 24 h after being given injections, they were sacrificed, and biodistribution studies were performed. Results of the study showed high kidney uptake [48.6% injected dose (ID)/g +/- 8.1% (SD)] and low tumor uptake (1.5% ID/g +/- 0.6%) for 99mTc(Sn)-labeled fragments and higher uptake (4.4% ID/g +/- 0.6%) for 131I-labeled fragments, resulting in a higher localization index for the radioiodinated monoclonal antibody fragments. Imaging results showed good tumor visualization at 24 h after injection for the 131I-labeled fragments and poor tumor visualization with predominant kidney uptake for 99mTc(Sn)-labeled fragments. After radiolabeling, high pressure liquid chromatography analysis indicated that 131I was primarily associated with F(ab')2 fragments, whereas 99mTc was mostly associated with Fab' fragments.

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Radioisotope scanning in inflammatory muscle disease.

Fourteen whole-body rectilinear bone scans using technetium 99m-polyphosphate were done in nine patients with well-documented inflammatory myopathy (either polymyositis or dermatomyositis). In all nine patients, the scans showed evidence of increased muscle labeling. Muscle uptake was markedly increased in one patient, moderately increased in two patients, and minimally increased in six patients. The degree of muscle labeling correlated with the severity of the muscle weakness at the time the scan was done. In four patients, who received high-dose corticosteroid treatment, muscle uptake was decreased following therapy. These findings suggest that radioisotope scanning may be useful in the diagnosis and management of patients with inflammatory muscle diseases.

A new radioisotope technique of splenic localization for radiation treatment.

A new technique of splenic localization, before initiating radiation therapy in patients with Hodgkin's disease, is described. We find this method of splenic localization economical and accurate.

The paper spot test: a rapid method for quantitating stannous concentrations in radiopharmaceutical kits.

We have developed a simplified, semiquantitative test for the determination of stannous tin in pyrophosphate and other tin-containing radiopharmaceuticals, excluding those stabilized with ascorbic acid and MAA preparations. The test involves the formation and disappearance of a positive red color complex in the presence of Sn(II) and in acidified porphyrin solution. With this technique, the time of spot disappearance is directly proportional to the Sn(II) concentration spotted. The procedure is easy to use, requiring only a high-intensity light source (30-watt light bulb) and a timing device. The test is accurate, reproducible, and sensitive to Sn(II) levels as low as 40 micrograms/ml. Because the procedure is rapid (requiring less than 5 min), it can easily be incorporated into the routine radiopharmaceutical quality-control program of any nuclear medicine facility.

Increased 99mTc-polyphosphate muscle uptake in a patient with polymyositis: case report.

A patient with well-documented rheumatoid arthritis and polymyositis displayed abnormal muscle uptake of 99mTc-polyphosphate during routine bone scanning for occult malignancy. The regions of increased uptake corresponded to the areas of clinically active inflammatory muscle disease. On serial scans the degree of muscle labeling correlated well with both clinical and laboratory indices of disease activity.

A case of myocardial abscess evaluated by radionuclide techniques: case report.

A patient with infective endocarditis was evaluated by Ga-67 citrate imaging, Tc-99m pyrophosphate imaging, equilibrium gated blood pool imaging, and Tl-201 imaging of the chest. The diagnosis of ventricular abscess was first suggested by an abnormal gallium scan. At surgery, an abscess was identified in the area where the scan was abnormal, and postoperatively a repeat scan was normal.

Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of retreatment following plasmapheresis.

Radioimmunotherapy retreatment of patients receiving radiolabeled murine monoclonal antibodies is difficult because of human antimurine antibody (HAMA) formation. Retreatment therapy was initiated in three patients at the time of disease progression using a radioiodinated monoclonal antibody (T101). The clinical protocol consisted of a two day plasma exchange (4-6 L) to reduce HAMA titers. Immunoimaging was performed with 5 mCi 131I-T101 (10 mg). Gamma scintillation images were obtained 18 hr postinfusion, and radiation dosimetry estimates were performed. At 24 hr postinfusion, each patient received a 100-mCi 131I-T101 (10 mg) therapy dose. Results obtained after plasmapheresis showed a significant reduction, ranging from 28%-61%, in HAMA titers. Blood clearances were markedly different between initial therapy and retreatment therapy for patient with high HAMA titers, reflecting immune complex formation. Two patients responded to retreatment therapy with responses lasting 1 to 2 mo. Minimal acute and no chronic toxicities were observed during the retreatment protocol.

Planar imaging versus gated blood-pool SPECT for the assessment of ventricular performance: a multicenter study.

UNLABELLED: Gated blood-pool SPECT (GBPS), inherently 3-dimensional (3D), has the potential to replace planar equilibrium radionuclide angiography (ERNA) for computation of left ventricular ejection fraction (LVEF), analysis of regional wall motion (RWM), and analysis of right heart function. The purpose of this study was to compare GBPS and ERNA for the assessment of ventricular function in a large, multicenter cohort of patients. METHODS: One hundred seventy-eight patients referred in the usual manner for nuclear medicine studies underwent ERNA followed by GBPS. Each clinical site followed a GBPS acquisition protocol that included 180 degrees rotation, a 64 by 64 matrix, and 64 or 32 views using single- or double-head cameras. Transverse GBPS images were reconstructed with a Butterworth filter (cutoff frequency, 0.45-0.55 Nyquist; order, 7), and short-axis images were created. All GBPS studies were processed with a new GBPS program, and LVEF was computed from the isolated left ventricular chamber and compared with standard ERNA LVEF. Reproducibility of GBPS LVEF was evaluated, and right ventricular ejection fraction (RVEF) was computed in a subset of patients (n = 33). Using GBPS, RWM and image quality from 3D surface-shaded and volume-rendered cine displays were evaluated qualitatively in a subset of patients (n = 30). RESULTS: The correlation between GBPS LVEF and planar LVEF was excellent (r = 0.92). Mean LVEF was 62.2% for GBPS and 54.1% for ERNA. The line of linear regression was GBPS LVEF = (1.04 x ERNA LVEF) + 6.1. Bland-Altman plotting revealed an increasing bias in GBPS LVEF with increasing LVEF (Y = 0.13x + 0.61; r = 0.30; mean difference = 8.1% +/- 7.0%). Interoperator reproducibility of GBPS LVEF was good (r = 0.92). RVEF values averaged 59.8%. RWM assessment using 3D cine display was enhanced in 27% of the studies, equivalent in 67%, and inferior in 7%. CONCLUSION: GBPS LVEF was reproducible and correlated well with planar ERNA. GBPS LVEF values were somewhat higher than planar ERNA, likely because of the exclusion of the left atrium.

Hemophilic bleeding evaluated by blood pool scanning.

The technique of blood pool scanning was used to examine 15 hemophilic subjects. Employing an in vivo method for erythrocyte labeling with Technetium-99 m, a dynamic perfusion sequence is obtained using a scintillation camera positioned over the area to be examined. This demonstrates the vascularity of the tissue. Subsequently, equilibrium blood pool images of the area are obtained and analyzed with a densitometer to assess relative regional blood volume. In patients who were not bleeding but had chronic arthropathy, vascularity was not increased, and the blood volume of comparable joints was similar. By contrast, marked increases in vascularity and image density were observed in studies of acutely bleeding joints. Chronic hemarthroses were associated with persistent, but less marked increases in joint perfusion. Transient increases in joint vascularity were demonstrated after insertion of knee prostheses. In a patient with a thigh hematoma, the dimensions of the hemorrhage were clearly delineated. Since only a tracer dose of nuclide is infused intravenously, there are no allergic reactions or other side effects of the procedure. Blood pool scanning is a safe, non-invasive technique that augments clinical and radiographic evaluations, and provides a new dimension in the assessment of the hemophilic patient.

Usefulness of single-photon emission computed tomography of thallium-201 uptake after dipyridamole infusion for detection of coronary artery disease.

The diagnostic performance of single-photon emission computed tomography (SPECT) and planar imaging of thallium-201 uptake for the detection of coronary artery disease (CAD) was compared in 79 patients who underwent both dipyridamole thallium-201 scintigraphy and coronary angiography. Clinical subgroups were assigned by severity of CAD, presence of a prior myocardial infarction and the number of narrowed coronary arteries. The overall detection of CAD was 89% for SPECT and 67% for planar (p less than 0.001). For the anterior vascular territory, sensitivities for SPECT and planar imaging were 69 and 44% (p less than 0.01), respectively; for the posterior vascular territory, sensitivities were 80 and 54% (p less than 0.01). Receiver-operating characteristic analysis, using a 5-point evaluation scale, was performed for the anterior and posterior vascular territories. Receiver-operating characteristic curves generated for SPECT and planar studies demonstrated improved diagnostic performance by SPECT in the anterior vascular territory, but showed similar performance in the posterior territory because of lower SPECT specificity despite higher sensitivity at clinically relevant decision thresholds. In each clinical subgroup of patients, the detection of CAD by SPECT was significantly superior to that by planar imaging, regardless of the severity of stenosis or the number of significantly narrowed coronary arteries, or whether a myocardial infarction was present. Thus, SPECT thallium-201 scintigraphy is an important and necessary clinical tool for detecting CAD after dipyridamole infusion.

Considerations for tomographic imaging of monoclonal antibodies.

Monoclonal antibodies have begun to assume a significant role in clinical research. The ability to label these agents has initiated research in the areas of radioimmunodetection and radioimmunotherapy. In the case of antibodies directed against tumor antigens, imaging has been employed to help assess location and extent of disease, and to provide information and extent of disease, and to provide information concerning biodistribution to be used in subsequent dosimetric calculations. Because of the low counting statistics characteristic of such images, the use of single photon emission computed tomography (SPECT) is suggested as a potential method of improving the diagnostic yield from image data. Careful attention to acquisition parameters and image processing options is needed if these goals are to be achieved.

Nuclear medicine imaging workstations based on personal computer technology.

The development of personal computer technology has resulted in extremely powerful, inexpensive computers available as consumer items. With the addition of suitable hardware for gamma camera interfacing and image display, such systems can be transformed into fully functional nuclear medicine computers capable of performing all of the acquisition and processing tasks required in a modern radioisotope imaging department. Such an approach to nuclear medicine computerization offers many advantages in terms of flexibility, speed, cost, and expandability.

Serial assessment of left ventricular performance following coronary artery bypass grafting. Early postoperative results with myocardial protection afforded by multidose hypothermic potassium crystalloid cardioplegia.

Forty patients who recently underwent coronary artery bypass graft (CABG) operations had serial hemodynamic and scintigraphic studies. Multidose hypothermic potassium crystalloid cardioplegia was used for myocardial protection and newer techniques in anesthetic management and perioperative patient care were also employed. The method of equilibrium cardiac gated blood pool (GBP) scintigraphy was used to obtain perioperative changes in global ejection fraction (EF) and regional wall motion (RWM). Ninety percent of patients displayed a decrease in EF 2 hours postoperatively when compared to their preoperative values. This change was also associated with a fall in cardiac index (CI) and left ventricular stroke work index (LVSWI). Twenty-four hours postoperatively, EF and CI recovered to preoperative levels, but LVSWI remained depressed. Seven days postoperatively, global EF had improved to a value greater than the preoperative one (50% +/- 3% versus 57% +/- 4%, p < 0.05). Perioperative changes in RWM followed the same pattern as EF, but recovery in this index of regional contractility was faster than EF, since maximal improvement was observed 24 hours postoperatively. Thus transient left ventricular dysfunction is common immediately after CABG, but recent advances in myocardial protection and perioperative management are associated with short-term increases in regional and global left ventricular function documented by noninvasive GBP imaging.

Early and long-term improvement in left ventricular performance following coronary bypass surgery.

Changes in left ventricular performance after coronary artery bypass grafting (CABG) have been variable. Earlier studies based on contrast left ventriculography have shown occasional improvement in left ventricular function in patients with unstable angina or abnormal preoperative ventricular performance, but for the most part repeat cardiac catheterization several months after operation has shown no significant changes in global left ventricular contraction. In the past few years, advances in radiopharmaceutical technology have made the characterization of left ventricular wall motion accurate and highly reproducible. Since prognosis in patients with coronary artery disease and survival after CABG have been related to global ejection fraction (EF), we employed prospectively on analysis of short-term and long-term changes in EF after CABG utilizing multidose hypothermic potassium crystalloid cardioplegia as the method of myocardial protection. Concomitantly, newer techniques in anesthesia and perioperative patient management were employed to minimize myocardial damage in these patients. Postoperative scintigraphic evaluation showed a transient (2-hour) depression in left ventricular function, followed by recovery to preoperative levels at 24 hours and significant improvement in EF at 7 days. From 7 days to 8 months postoperatively, there was no further change in resting EF, but there was another significant exercise-induced increase in EF at the long-term examination. Thus, present advances in the multidisciplinary management of patients with coronary artery disease are associated with improvement in resting and exercise-related EF postoperatively.

Changes in left ventricular performance related to perioperative myocardial infarction in coronary artery bypass graft surgery.

Strict electrocardiographic, enzymatic, scintigraphic, and hemodynamic criteria for perioperative myocardial infarction (MI) were defined and related to serial assessments of left ventricular performance during rest and exercise in patients seen early and late after coronary artery bypass graft operation. Global left ventricular performance was determined by radionuclide ventriculography from which changes in the pattern of serial postoperative ejection fractions (EF) were obtained. Patients were divided into two groups based on the presence or absence of perioperative MI, and were matched in pairs on the basis of preoperative EF and extent as well as location of coronary artery obstructions. The results indicate that neither short- nor long-term depression in resting EF occurred subsequent to perioperative MI. However, an exercise-related increase in EF eight months postoperatively was depressed in patients who had perioperative MI compared with those who did not. Patients with new Q waves and abnormal postoperative elevation in serum levels of the myocardial isoenzyme of creatine kinase (CK-MB) had a greater early decrease in EF compared with patients without evidence of perioperative MI. However, seven days after operation, the EF in both groups returned to preoperative levels. Patients with abnormal technetium 99m-pyrophosphate scintigrams had changes in perioperative EF similar to those in patients without MI. The presence of low cardiac output syndrome immediately after operation was associated with immediate and short-term decreases in EF, which were not seen in any of the other patient subgroups.

Clinical evaluation of the relative effectiveness of multidose crystalloid and cold blood potassium cardioplegia in coronary artery bypass graft surgery: a nonrandomized matched-pair analysis.

Controversy exists concerning the most effective method of myocardial protection during coronary artery bypass graft operations. Accordingly, we performed a matched-pair analysis between 25 patients receiving multidose hypothermic potassium crystalloid cardioplegia and 25 other patients receiving cold blood potassium cardioplegia. Patients were matched on the basis of preoperative ejection fraction (EF) and the number of anatomically similar stenotic coronary arteries. The adequacy of myocardial protection was assessed by serial perioperative determinations of radionuclide ventriculography, hemodynamic measurements, analyses of electrocardiograms and serum levels of MB-CK. We found that the level of myocardial protection was similar between unstratified groups. However, when subgroups were selected on the basis of prolonged aortic cross-clamp time (greater than ninety minutes) or impaired preoperative left ventricular function (EF less than 40%), there was a suggestion that cold blood cardioplegia may be advantageous.

Nonrandomized matched pair analysis of intermittent ischemic arrest versus potassium crystalloid cardioplegia during myocardial revascularization.

The quest for the ideal method of myocardial preservation during coronary artery bypass graft (CABG) surgery continues at a rapid pace. Nevertheless, in the present clinical practice of cardiac surgery, the choice is chiefly between hypothermic intermittent ischemic arrest and hypothermic potassium cardioplegia. This study applies newer technics in radionuclear cardiology, as well as more conventional enzymatic, electrocardiographic, and hemodynamic determinations, to the evaluation of the effectiveness of the previously mentioned modes of myocardial protection. Serial assessments are made preoperatively as well as during the first ten days postoperatively. We find that the perioperative incidence of myocardial damage and changes in left ventricular performance are almost identical using either method in patients with relatively normal preoperative left ventricular performance who do not have severe preoperative refractory ischemia or necrosis.

Correlation of marrow dose estimates based on serial pretreatment radiopharmaceutical imaging and blood data with actual marrow toxicity in anti-CD20 yttrium-90 monoclonal antibody radioimmunotherapy of non-Hodgkin's B-cell lymphoma.

The purpose of this study was to investigate whether marrow radiation absorbed dose estimates predict haematotoxicity following radioimmunotherapy with an yttrium-90 labelled anti-CD20 monoclonal antibody in non-Hodgkin's B-cell lymphoma (NHL). Radiopharmaceutical data from 12 NHL radioimmunotherapy patients were analysed retrospectively using three methods of marrow radiation absorbed dose estimation based on serial pretreatment indium-111 labelled anti-CD20 monoclonal antibody activity versus time data (0-144 h): (i) lumbar spine (LS) image counts; (ii) blood clearance (BL); and (iii) whole body (WB) activity. Linear regressions were performed between the methods, and between each method and the 0-6 month post-treatment platelet and white blood cell count nadir and absolute drop in count (ADC). For the range of yttrium-90 activities (740-1547 MBq), absorbed dose estimates (mean +/- sigma) were: LS, 142+/-50 cGy (range 62-233 cGy); BL, 89+/-21 cGy (range 63-140 cGy); and WB, 54+/-10 cGy (range 36-63 cGy). The LS and BL marrow estimates differed significantly (P <0.003), with a correlation coefficient r of 0.36 (P = NS), while WB correlated significantly with both LS (r = 0.50, P < 0.05) and BL (r = 0.58, P < 0.05). The range of r with platelet nadir and ADC was -0.20 < or = r < or = 0.01, except for WB with ADC (r = 0.38) (all P = NS). Values of r for white blood cell nadir were unexpectedly positive, being 0.13 for BL and 0.29 for LS (P = NS), and 0.60 for WB (P < 0.025). Values of r for white blood cell ADC were 0.36 for BL and -0.26 for LS (P = NS), and 0.50 for WB (P < 0.05). These results indicate that different commonly employed methods of estimating marrow radiation absorbed dose may yield significantly differing results, which may not correlate with actual radiation toxicity. Therefore, caution must be exercised in relying on these results to predict haematotoxicity.