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Biomedical subjects

S M Spies

Publications and source records attributed to S M Spies.

At least 19 recordsLinked to original sources

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.

Algorithms↗

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.

Gated Blood-Pool Imaging↗

The effect of remifentanil on biliary tract drainage into the duodenum.

UNLABELLED: Opioids cause spasm of the sphincter of Oddi. Remifentanil is metabolized enzymatically throughout the body. Its context-sensitive half-time is 3-4 min. The effect of remifentanil on the sphincter of Oddi, is unknown. We studied, in six healthy adult volunteers, the effect of remifentanil on the flow of dye from the gall bladder into the duodenum. Control hepatobiliary imaging with 5 mCi of technetium-labeled derivatives of iminodiacetic acid was performed on each volunteer. The time from IV dye (radiopharmaceutical) injection until its appearance in the duodenum was determined by continuous scanning. Two weeks later, each volunteer received remifentanil, 0.1 microg x kg(-1) x min(-1) infused for 30 min IV before the same dose of technetium-labeled derivatives of iminodiacetic acid was injected, and for the time of their control scan plus 10 min after the injection. When the dye appeared in the duodenum, the total time from injection was compared with the control value. The time from stopping the infusion until the dye appeared in the duodenum was the "recovery time." Control scan time was 20.5+/-9.9 min (mean +/- SD; range 10-33 min). Total scan time during and after the remifentanil infusion was 50.3+/-17.3 min (range 30-81 min) (P < 0002). The recovery time was 19.8+/-12.4 min (range 5-40 min). We conclude that remifentanil delays the drainage of dye from the gall bladder into the duodenum, but the delay is shorter than that reported after other studied opioids. IMPLICATIONS: Radioactive dye was injected IV into healthy volunteers to determine the time it took for the dye to appear in the duodenum. This was repeated under the influence of a short-acting narcotic analgesic, remifentanil. Remifentanil caused a much shorter delay than previously reported after morphine or meperidine.

Adult↗

Rapid miniaturized chromatography for technetium-99m-tetrofosmin.

UNLABELLED: The purpose of this investigation was to develop and evaluate a new and rapid miniaturized chromatography system that would accurately assess the radiochemical purity of 99mTc-tetrofosmin without the problems of solvent ratios and time requirements associated with the manufacturer's recommended procedure. METHODS: The migration of the radiochemical components of 99mTc-tetrofosmin was evaluated using various chromatography media with ethyl acetate as the solvent. After optimization of the miniaturized system, radiochemical purity assessments were performed simultaneously on 23 99mTc-tetrofosmin preparations using both recommended and miniaturized chromatography systems. RESULTS: A miniaturized chromatography system consisting of Whatman 1 chromatography paper with ethyl acetate was developed for the radiochemical purity assessment of 99mTc-tetrofosmin. Radiochemical purity results for 99mTc-tetrofosmin preparations were similar with both recommended and miniaturized chromatography methods, with a mean difference of 1.5% +/- 1.2% (s.d.). Differences in radiochemical purity results between the two chromatography systems were less than 2% (20 of 23 evaluations) with most preparations. CONCLUSION: Radiochemical purity results for 99mTc-tetrofosmin preparations were similar with both the manufacturer's recommended chromatography and miniaturized chromatography systems. The miniaturized chromatography system is easier to use, and the time required to perform radiochemical purity assessments is substantially reduced.

Acetates↗

Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma.

BACKGROUND: This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperthermia in patients with metastatic colorectal adenocarcinoma. METHODS: Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperthermia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti-CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetic clearance data were reported for all nine patients. RESULTS: Thermometry data revealed an average T90 of 40.3 (+/- 1.4 degrees C) and T50 of 41.1 (+/- 1.2 degrees C). The average thermal dose equivalent at 42.5 degrees C was 34.5 (+/- 21.5) minutes. The average Tmin, Tmax, and Tmeam were 40 (+/- 1.2 degrees C), 42.4 (+/- 0.7 degrees C), and 41.1 (+/- 1.1 degrees C), respectively. The pharmacokinetic clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS: It is feasible to combine hyperthermia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperthermia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combined modality in the management of maligancies.

Adult↗

Reinfusion of postoperative wound drainage in total joint arthroplasty. Red blood cell survival and coagulopathy risk.

Fifty patients with total joint arthroplasties (28 total hip arthroplasties, 11 total knee arthroplasties, and 11 bilateral total knee arthroplasties) received autotransfusions from their postoperative wound drainage. The blood was collected in a closed sterile drainage system without any additional anticoagulant. Pre- and postoperative measurements were made of the patient's hemoglobin, platelets, fibrinogen, haptoglobin, fibrin degradation products, and D-dimer (a specific type of fibrin degradation product). Red blood cell survival was assessed in 16 of the patients by labeling the shed blood with 51Cr sodium chromate prior to reinfusion. To control for fluid shifts, continued bleeding, and dilution effects of further transfusions in the immediate postoperative period, 10 patients also had their native blood labeled with 111In oxime. In this study, the mean estimated blood loss was 1,062 mL (+/- 1,247) with a mean wound drainage of 836 mL (+/- 338). Of this, a mean of 450 mL (+/- 261) of blood was was given back to the patient in addition to routine, preoperative autologous donated blood. Six (12%) patients experienced transient fevers at the time of retransfusion. Detailed hematologic studies were performed on the shed blood in 19 patients. The collected blood was completely defibrinated, but did contain fibrin degradation products, as indicated by the D-dimer level, and hemolyzed blood as the haptoglobin was reduced. Even though the blood containing the above breakdown products was reinfused to the patients, there were no clinical manifestations of disseminated intravascular coagulation. Both the hemolyzed and defibrinated products were subsequently cleared by the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗

Effects of hyperthermia and iodine-131-labeled anticarcinoembryonic antigen monoclonal antibody on human tumor xenografts in nude mice.

BACKGROUND: Many studies have demonstrated synergistic interaction between hyperthermia and radiation. This study was undertaken to determine whether hyperthermia could enhance the effect of radioimmunotherapy (RIT) in the treatment of human colon adenocarcinoma xenografts in nude mice. METHODS: The experiments were conducted in two parts. During the first part of the study, preliminary information was obtained regarding the effect of various temperatures (41 degrees C, 42 degrees C, and 43 degrees C for 45 minutes) and iodine-131-labeled anticarcinoembryonic antigen (CEA) monoclonal antibodies (RMoAb) with administered activity ranging from 130 +/- 19 microCi to 546 +/- 19 microCi on tumor regrowth delay (TRD) and volume doubling time. This information was used in Part 2 of the study, which included four groups of mice: (1) a control group, (2) a group treated with hyperthermia, (3) a group treated with RMoAb, and (4) a group treated with a combination of RMoAb and hyperthermia. RESULTS: Maximum and significantly increased TRD was observed in the group treated with RMoAb and hyperthermia (slope, 0.057) compared with the control group (slope, 0.322), the hyperthermia-treated group (slope, 0.302), and the group treated with RMoAb alone (slope, 0.098). The ratio of the slopes between the groups treated with RMoAb and those treated with RMoAb and hyperthermia was 1.72. No correlation was detected between the percent of antibody uptake in the tumor and tumor regression in the groups treated with heat and RMoAb and those treated with RMoAb alone. CONCLUSIONS: The results of these experiments show that hyperthermia increased the effectiveness of iodine-131-labeled anti-CEA monoclonal antibodies against human colon carcinoma xenografts in nude mice. This study offers a rationale for combining hyperthermia and low-dose radiation produced from RIT in clinical practice.

Adenocarcinoma↗

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.

Adult↗

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.

Hospital Departments↗

Stability of radioiodinated monoclonal antibodies: in vitro storage and plasma analysis.

The in vitro stability and immunointegrity of four radioiodinated monoclonal antibodies was evaluated in various storage conditions and also in plasma samples. The monoclonal antibodies studied included T101, B72.3, Lym1, and 16.88. Stabilities of typical monoclonal antibody therapy solutions, with radioactivities ranging from 2220 to 3700 MBq (60-100 mCi) were assessed using conventional instant thin layer chromatography and size exclusion high performance liquid chromatography. Radioimmunoreactivity was assessed using a live cell attenuated cell, or mucin-linked bead assay. Results of the study demonstrated that therapy solutions were stable to degradation, if properly stored in 5 or 10% human serum albumin at 4 degrees C for the duration of the study (5 days). Minor losses in immunoreactivity were also measured in stabilized therapy solutions. When incubated in plasma samples, radioiodinated monoclonal antibodies generally remained stable for the duration of the study (3 days). However, significant decreases in immunoreactivity were measured for specific radioiodinated monoclonal antibody preparations.

Antibodies, Monoclonal↗

Value of post-therapy whole-body I-131 imaging in the evaluation of patients with thyroid carcinoma having undergone high-dose I-131 therapy.

Post-therapy whole-body I-131 images were compared to 5 mCi pretherapy diagnostic studies in 39 cases of well-differentiated thyroid carcinoma treated with I-131 to evaluate the utility of this procedure for the detection of residual thyroid tissue and functioning metastases. The post-therapy studies were performed immediately before hospital discharge, when the patient's whole-body retained dose had just fallen below 30 mCi. The mean therapeutic dose given was 121 mCi, and the mean interval between administration of the therapy dose and imaging was 2.4 days. In 18 cases (46.2%), the post-therapy images demonstrated either additional findings, such as unsuspected cervical node or pulmonary uptake, or more accurate localization of abnormalities seen on the diagnostic study. In 6 additional cases (15.4%), questionable new findings were noted. Although the precise implications of these additional findings are uncertain at present, they may have a significant effect on future patient management and follow-up. Therefore, the authors recommend that post-therapy imaging be included in the post-therapy evaluation of these patients. In addition, these findings would also suggest reevaluation of the advisability of using 1-2 mCi doses of I-131 for diagnostic whole-body imaging.

Adenocarcinoma↗

Rapid miniaturized chromatography for 111In labeled monoclonal antibodies: comparison to size exclusion high performance liquid chromatography.

Our laboratory investigated the use of a rapid miniaturized chromatography system, ITLC-SG with 0.9% NaCl, to assess the radiochemical purity of 111In labeled monoclonal antibodies (MoAbs). Radiochemical analysis was performed on numerous 111In labeled antibody preparations with labeling efficiencies ranging from 40 to greater than 95% and the results compared to those obtained with size exclusion high performance liquid chromatography (HPLC). The chromatographic procedure involved challenging radiolabeled antibodies with 0.05 M DTPA to chelate unbound and/or non-specific bound 111In, spotting on miniaturized instant thin layer-silica gel chromatography strips, developing in 0.9% NaCl, and counting appropriate segments for radioactivity. Results of the study demonstrated that the miniaturized chromatography procedure was rapid, taking less than 4 min to complete, and accurate in assessing the amount of unbound or non-specific bound 111In in 111In labeled monoclonal antibodies, when compared to size exclusion HPLC.

Antibodies, Monoclonal↗

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.

Antibodies, Monoclonal↗

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.

Animals↗