Renal function studies using 99mTc-MAG3: pharmacokinetics and slope clearance determination.
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Humans↗
Biomedical subjects
P Georgi
Publications and source records attributed to P Georgi.
Pharmacokinetics of technetium-99m-MAG3 in humans.
Technetium-99m-mercaptoacetylglycylglycylglycine (99mTc-MAG3) is introduced to replace o-iodohippurate (OIH) for renal function studies. For interpretation of clinical findings, extensive pharmacokinetic studies were performed on patients. These showed that 99mTc-MAG3, compared with OIH, has a higher plasma-protein binding, an essentially higher intravascular concentration, a smaller volume of distribution and, with practically identical biologic half-lives, a correspondingly lower clearance. Simultaneous steady-state measurements resulted in a 1.5-fold higher clearance of OIH than of 99mTc-MAG3 (n = 124). Competitive inhibition of the tubular transport system by p-aminohippurate (PAH) (20 patients) revealed a distinctly higher suppression of the 99mTc-MAG3 clearance than of OIH which indicates a lower affinity of the 99mTc complex to the tubular cell. The plasma extraction efficiencies of both agents, measured during surgery (n = 5), did not indicate an extrarenal elimination of 99mTc-MAG3. This new radiopharmaceutical is a pragmatic alternative to OIH and offers advantages not only for scintigraphic imaging but is also suited for quantitative renal function studies.
Humans↗
Current status of immunoscintigraphy in colorectal cancer--results of 5 years' clinical experiences.
In 100 patients with suspected colorectal cancer, findings of conventional diagnostic methods were compared with immunoscintigraphy results. In a first trial 131-J-labelled F (ab') 2-fragments against CEA and CA 19-9 were used in 42 patients. Evidence was confirmed by surgical exploration in 69% of cases and by close follow-up examination in 31%. In a second trial 58 patients were included, and 81% of these were explored surgically. Conventional diagnostic methods achieved better results in both series in imaging liver and extrahepatic tumor manifestations, and in both series immunoscintigraphy was especially disappointing with regard to extrahepatic tumor diagnosis (sensitivity 23% and 38%, respectively). Accuracy could not be improved by technical modifications such as change of antibodies, radiolabels or imaging techniques. The value of immunoscintigraphy as a helpful tool for the operative management of metastatic or recurrent colorectal cancer must, therefore, be viewed critically.
Antibodies, Monoclonal↗
The value of immunoscintigraphy for the operative retreatment of colorectal cancer. Limitations of a new diagnostic method.
In 42 patients with suspected recurrent colorectal cancer, results of conventional diagnostic methods were compared with those of immunoscintigraphy. In 69% of all cases, the intraoperative findings of a second-look operation served for validation, whereas in 31% close follow-up was used. Recurrent tumors were successfully localized in 83% of patients by conventional methods, whereas immunoscintigraphy was expressive in 57% of cases. Immunoscintigraphy was disappointing especially because of its low sensitivity (23%) and low predictive value (positive, 33%; negative, 37%) with regard to successful diagnosis of extrahepatic tumors compared with the results of conventional methods (77% sensitivity; positive, 94%; negative, 79%). The rate of false-positive results was relatively high with immunoscintigraphy (n = 12), 83% of which were related to extrahepatic recurrent tumors. The value of immunoscintigraphy using an immunococktail of 131-J-labeled F(ab')2 fragments of monoclonal antibodies against CEA, with Ca 19-9 as an additional diagnostic tool for early detection of recurrent colorectal cancer, must therefore be viewed critically.
Antibodies, Monoclonal↗
[Hyperthyroidism caused by a hormone-producing follicular thyroid cancer].
A well differentiated carcinoma of the thyroid is usually less productive with respect to thyroid hormones than normal thyroid tissue. Very rarely, it happens though that a metastatic follicular carcinoma of the thyroid produces hyperthyroidism as the following example illustrates. In our patient with follicular thyroid carcinoma the radioiodine scan demonstrated an increased uptake of 123I in the right thyroid lobe but also in a lung metastasis, even before thyroidectomy. In contrast, the iodine uptake of the left - normal - thyroid lobe was suppressed. Following thyroidectomy the levels of the thyroid hormones were normal and only dropped into the hypothyroid range after the beginning of the therapy with radioiodine. Hence we conclude that the metastases of a thyroid carcinoma can attain the hormone secretion of a normal thyroid gland and take up more radioiodine than normal thyroid tissue.
Adenocarcinoma↗
Scar or recurrent rectal cancer. Positron emission tomography is more helpful for diagnosis than immunoscintigraphy.
We used positron emission tomography and fludeoxyglucose F 18 to assess metabolic activity of a pelvic mass in 18 patients who had suspected recurrent rectal cancer. Computed tomography could not differentiate tumor from scar. All patients presenting increased uptake of fludeoxyglucose F 18 by the mass were proved by histologic studies to suffer from recurrent tumor. Six of seven patients with low fludeoxyglucose uptake had nonmalignant lesions. Using immunoscintigraphy in 14 patients with elevated carcinoembryonic antigen levels, only four of ten recurrences could be identified by increased antibody accumulation in the mass. On the other hand, two of four benign lesions were interpreted as being recurrent tumor because of high uptake. Therefore, only positron emission tomography seems to be a useful diagnostic tool in the differentiation of recurrent rectal cancer and scar by providing information about the metabolic activity of a mass.
Antibodies, Monoclonal↗
Regional cerebral blood flow in endogenous psychoses: a Tc-99m HMPAO-SPECT pilot study.
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Cerebral Cortex↗
[Does immunoscintigraphy improve early diagnosis of metastatic or recurrent cancer?].
In 42 patients with suspicion of recurrent colorectal cancer results of conventional diagnostic methods were compared to those of immunoscintigraphy. In 69% of all cases the intraoperative findings of a second-look operation served for validation, in 31% the follow-up was controlled. Localization of recurrent tumors was successful in 83% using conventional methods versus 57% by immunoscintigraphy. This procedure disappointed especially by a low sensitivity (23%) and low predictive parameters (pos.: 33%; neg.: 37%) in regard to diagnosis of extrahepatic tumors compared to results of conventional methods (77%), 94% respectively 79%). The quote of false positive results was surprisingly high in immunoscintigraphy (n = 12), 83% of these especially in localization of extrahepatic tumors. Therefore, the validity of immunoscintigraphy as an additive diagnostic tool for early detection of recurrent colorectal cancer must be regarded critically.
Antibodies, Monoclonal↗
[Re: 57Co-bleomycin scintigraphy for the preoperative detection and staging of lung tumors].
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Bleomycin↗
[Radiologic diagnosis of bone metastases].
The diagnostic relevance of the various radiological examination methods - skeleton scintigraphy, conventional x-ray film, computed tomography, sonography and magnetic resonance - was analysed on the basis of an examination of 4765 clinically or scintigraphically suspect skeleton segments in order to arrive at an effective but also economically justifiable diagnostic approach. Conventional skeleton scintigraphy should be employed as the first method of choice, since it has a sensitivity of 93% and is hence very suitable as a searching tool. To differentiate benign and malignant lesions it is absolutely imperative to conduct at the same time a x-ray control of any abnormal accumulation of nuclides, or of parts of the skeleton that display signs or symptoms. Conventional x-ray film diagnosis enabled correct diagnosis of the type of disease in 95% of the cases. In its capacity as a complementary examination method, computed tomography enabled correct diagnosis in 52% of the cases that had remained roentgenologically unclear. A pathological bone scintigram without any x-ray or CT correlate must be considered as being suspect of metastases if trauma is absent. Magnetic resonance proved to be the most sensitive method in identifying malignant infiltrations of the medullary space in two patients suffering from a clearly delineated pain syndrome with normal x-ray and CT findings. Sonography proved superior in detecting extraosseous tumour portions. The value of angiography is the preoperative vascular imaging of metastases of the possibility of performing therapeutic embolisation or intraarterial drug therapy.
Angiography↗
[Effects of gallopamil on iodine-123-phenyl-pentadecanoic acid and thallium 201 uptake in patients with coronary heart disease].
Numerous experimental and clinical studies indicated that in the presence of coronary artery stenoses, myocardial thallium-201 and free fatty acid uptake in poststenotic regions is reduced during exercise. The aim of this study was to investigate the effect of the calcium antagonist gallopamil on myocardial thallium-201 and free fatty acid uptake in patients suffering from coronary artery disease. In 6 patients with angiographically proven coronary artery disease--2 patients with 1-vessel, 2 patients with 2-vessel and 2 patients with 3-vessel disease--as well as good left ventricular performance and stable, exerciseinduced angina, quantitative double-tracer scintigraphy was performed. Patients were investigated after a placebo period of 1 week, after oral gallopamil medication for 4 weeks (3 X 50 mg gallopamil daily), and after a double-blind period of 1 week. During symptom-limited exercise, 2 mCi thallium-201 and 5 mCi iodine-123 phenyl-pentadecanoic acid (IPPA) were simultaneously injected intravenously. Immediately after exercise, as well as 1 and 4 hours later, planar images were obtained in ap, 30 degrees LAO and 60 degrees LAO projections. By means of a newly developed computer algorithm, global and regional myocardial tracer uptake as well as IPPA clearance were evaluated. - Gallopamil provoked a decrease of global myocardial thallium-201 and IPPA uptake due to a reduction of myocardial oxygen consumption. Regional thallium-201 and IPPA uptake as well as myocardial IPPA clearance in poststenotic areas tended to rise following gallopamil medication. Thus, in the presence of coronary artery disease, gallopamil provokes an improvement of regional perfusion (dilatation of larger coronary arterioles) as well as an enhanced free fatty acid utilization in reversibly ischemic myocardial regions.
Angina Pectoris↗
[Preliminary results of 99mTc-HMPAO-SPECT studies in endogenous psychoses].
18 psychopharmacologically treated patients (7 schizophrenics, 5 schizoaffectives, 6 depressives) were studied using 99mTc-HMPAO-SPECT of the brain. The regional cerebral blood flow was measured in three transversal sections (infra-/supraventricular, ventricular) within 6 regions of interest (ROI) respectively (one frontal, one parietal and one occipital in each hemisphere). Corresponding ROIs of the same section in each hemisphere were compared. In the schizophrenics there was a significantly reduced perfusion in the left frontal region of the infraventricular and ventricular section (p less than 0.02) compared with the data of the depressives. The schizoaffectives took an intermediate place. Since the patients were treated with psychopharmaca, the result must be interpreted cautiously. However, our findings seem to be in accordance with post-mortem-, CT- and PET-studies presented in the literature. Our results suggest that 99mTc-HMPAO-SPECT may be helpful in finding cerebral abnormalities in endogenous psychoses.
Adult↗
[Diagnosis and therapy of differentiated thyroid cancer].
Summing up, we can state the following: Diagnosis of thyroid cancer seems easy, since the organ lies immediately beneath the skin, so that tumour growth could be readily detected, and also since thyroglobulin (tg) is an ideal and well-tried tumour marker. Nevertheless, malignant thyroid nodes are still frequently misinterpreted as benign, as benign strumae occur quite often. In view of the fact that malignant follicular carcinomas have a tendency to produce metastases via the bloodstream, in all tumours larger than 1 cm to 1.5 cm no change should be made in the classical therapeutic approach (total thyroidectomy, radioiodine therapy and levothyroxine suppression therapy), whereas in so-called occult papillary thyroid cancer (i.e. carcinomas smaller than 1-1.5 cm) hemithyroidectomy and lifelong suppression therapy can be satisfactory. It follows from this that in view of the low complication rate even with maximal therapy of differentiated thyroid cancer and the advantages resulting therefrom for follow-up care, the total ablation therapy should be retained as standard treatment. The low incidence of thyroid cancer justifies, inter alia, central follow-up care, the more so since this is usually performed on an interdisciplinary basis and there is as yet no standardised procedure for thyroglobulin determination.
Adenocarcinoma↗
Therapy of carcinoid tumors with [131I] meta-iodo-benzyl-guanidine.
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3-Iodobenzylguanidine↗
Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia.
The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.
Coronary Disease↗
Technetium-99m labeled renal function and imaging agents: I. Clinical evaluation of 99mTc CO2-DADS-A (99mTc N,N'-bis-(mercaptoacetyl)-2,3-diaminopropanoate).
Animal experiments and preliminary clinical results showed that the N2S2-complex 99mTc CO2-DADS-A, which was claimed to be a potential replacement for o-I-hippurate as a renal function agent, had a lower affinity for the tubular transport system than o-I-hippurate. In order to evaluate if this finding offered the possibility of detecting decreases in tubular function with more sensitivity, or at earlier times, 6 patients in the early post-transplantation period were subjected to 53 simultaneous scintigraphic investigations with 131I o-I-hippurate and 99mTc CO2-DADS-A. The comparison of the renograms obtained with the respective agents showed that in almost all cases of acute graft rejection only o-I-hippurate yielded the typical, diagnostically useful accumulation curve which results from its high retention in the kidney parenchyma. 99mTc CO2-DADS-A did not reveal this effect. Additionally the plasma clearance of each agent was measured simultaneously under steady state conditions in nine patients. Although it was reported that relative to o-I-hippurate the analog images obtained with 99mTc CO2-DADS-A gave higher kidney-to-background ratios and the amount excreted in the urine at 30 min was slightly less, the clearance values obtained for 99mTc CO2-DADS-A were on average only 36% of those for o-I-hippurate. It is concluded that 99mTc CO2-DADS-A is not suitable as a substitute for o-I-hippurate.
Alanine↗
Technetium-99m labeled renal function and imaging agents: II. Clinical evaluation of 99mTc MAG3 (99mTc mercaptoacetylglycylglycylglycine).
First clinical results indicated that among all potential 99mTc-complexes the N3S-complex 99mTc MAG3 has the biokinetic properties most similar to o-I-hippurate (OIH). A simultaneous comparison of 99mTc MAG3 and 131I OIH was conducted in a series of 48 patients. Twelve out of 18 transplant patients received simultaneously both radiopharmaceuticals for follow-up scintigraphic studies during the early post-transplantation period. In all of these double tracer studies (n = 90) the renograms obtained with 99mTc MAG3 exhibited qualitatively the same curve-shapes, compared with OIH, in cases of acute graft rejection or acute tubular necrosis. In addition, both agents were administered simultaneously to 46 of these patients and the plasma clearance values were determined under steady state conditions. The clearance data of both radio-pharmaceuticals showed a very good correlation (r = 0.95; P less than or equal to 0.05). The 99mTc MAG3/131I OIH clearance ratio showed a mean value of 0.65. Due to the high plasma protein binding of 99mTc MAG3 it is assumed not to be filtered through the glomerular membrane. Therefore we introduce for the 99mTc MAG3 clearance the term "Tubular Extraction Rate (TER)". Due to the favourable physical characteristics of 99mTc, higher activities can be administered as compared to 131I OIH. This allows the simultaneous examination of the tubular function as well as the renal perfusion. Additionally the kidney morphology is imaged with much better resolution. It is concluded that from the clinical point of view 99mTc MAG3 is a favourable replacement for OIH not only for renal imaging but also for the quantitative determination of tubular function. The acceptance will depend on the quality and on the handling of a commercially available kit formulation.
Animals↗
Comparative plasma thyroglobulin measurements with three non-cross-reactive monoclonal antibodies in metastatic thyroid cancer patients.
In 12 normal individuals and 25 patients with metastases of differentiated thyroid cancer, plasma thyroglobulin (Tg) concentrations were measured simultaneously with three immunoradiometric assays. Each of the three systems used a different, non-cross-reactive monoclonal Tg antibody as second antibody. In general, there was a very close correlation between the results of the three different systems in the cross-sectional study of the 25 cancer patients as well as in longitudinal follow-up studies in selected patients. The monoclonal antibody Tg 40 produced values about 30% higher than the two other systems. The difference was, however, not statistically significant owing to the large scatter. The monoclonal antibody Tg 13 appeared to be very sensitive to interference with thyroglobulin autoantibodies. In conclusion, the monoclonal antibodies against the three epitopes tested produced very similar Tg values in normal individuals and 25 patients with metastatic thyroid cancer; however, before more is known about epitope specificity of Tg autoantibodies and heterogeneity of tumour Tg, monoclonal antibodies should be used for routine measurements only with caution.
Antibodies, Monoclonal↗