Clinical value of a mucin-like carcinoma-associated antigen in monitoring breast cancer patients in comparison with CA 15-3.

A new tumour marker, mucin-like carcinoma-associated antigen (MCA), was evaluated in 176 breast cancer patients classified either as free of tumour (NED, n = 141) or as having metastases (PD, n = 35). During the 5 year follow-up, 842 measurements of MCA and 363 measurements of CA 15-3 were done. MCA levels were significantly increased in the PD group (P = 0.0001) but not in the NED group. The sensitivities of the MCA and the CA 15-3 assays were 84% and 78% and the specificities were 81% and 78%, respectively. The negative predictive value of 97% for MCA was significantly higher (P = 0.0001) than the 88% for CA 15-3. Thus the MCA enzyme immunoassay is at least equivalent to the CA 15-3 test and is recommended in the assessment of metastatic spread or tumour recurrence in breast cancer patients.

Different actions of deferoxamine and iron on Ga-67 abscess detection in rats.

The contrast-enhancing properties of iron (Fe) and deferoxamine (DFO) in abscess imaging with Ga-67 citrate were compared in rats bearing turpentine-induced abscesses. Iron administration shifted Ga-67 from plasma into tissues such as muscle and fat. As a result, the abscess-to-plasma ratio increased whereas the abscess-to-muscle ratio decreased. DFO enhanced the abscess-to-muscle and abscess-to-plasma ratios by increasing urinary Ga-67 excretion. In contrast to Fe, DFO removed abscess-bound Ga-67, thus representing a disadvantage of DFO compared with Fe. As a result, the abscess-to-plasma ratio was more effectively enhanced by Fe than by DFO. We conclude that abscess imaging with Ga-67 citrate may be improved by administration of Fe for detection of abscesses masked by blood activity, or DFO for detection of abscesses surrounded by muscle tissue.

Gallium-67/gallium-68-[DFO]-octreotide--a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies.

UNLABELLED: When labeled with gamma-emitting radionuclides, somatostatin analogs have the potential to localize somatostatin receptor-positive tumors using gamma camera scintigraphy. We present a somatostatin analog, [DFO]-octreotide (SDZ 216-927), that comprises desferrioxamine B coupled to octreotide via a succinyl linker. This conjugate can be labeled with either 67Ga for gamma scintigraphy or 68Ga for PET imaging. The 67Ga-labeled conjugate is stable in vitro to autoradiolysis over a 24-hr period. METHODS: Rats bearing a somatostatin receptor-positive pancreatic islet cell tumor were injected with 20 MBq of 67Ga[DFO]-octreotide (33 GBq 67Ga/mumole). RESULTS: After 1 hr, the accumulation of 67Ga[DFO]-octreotide was 0.38 +/- 0.08 %ID/g and the tumor-to-nontumor ratios for blood, muscle, liver and intestine were 2.5, 7.4, 1.9 and 1.6, respectively. PET studies with 68Ga[DFO]-octreotide recorded a very rapid accumulation at the tumor and a subsequent residence half-life of about 6 hr. CONCLUSION: Gallium-68-[DFO]-octreotide can be used in PET studies to diagnose receptor-positive tumors such as gastroenteropancreatic, small-cell lung and breast tumors.

Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging.

The biodistribution, dosimetry, and safety of a new myocardial imaging agent, 99mTc-hexakis-2-methoxyisobutyl isonitrile (HEXAMIBI), was evaluated in 17 normal volunteers at rest and exercise (Phase I studies). Technetium-99m HEXAMIBI clears rapidly from the blood with good myocardial uptake and favorable myocardial-to-background ratios for myocardial imaging. Dosimetry allows for administration of up to 30 mCi (1, 110 Bq) of [99mTc]HEXAMIBI. The myocardial images were of good quality and appeared less granular with sharper myocardial walls compared to 201T1 images. The clinical efficacy of [99mTc]HEXAMIBI planar stress and rest imaging was evaluated in a multicenter Phase II clinical trial involving 38 patients. Of 36 patients with significant coronary artery disease, 35 patients (97%) had abnormal 201T1 stress images, and 32 (89%) had abnormal [99mTc]HEXAMIBI stress images (P = N.S.). Technetium-99m HEXAMIBI images correlated in 31/35 patients (86%) who had either scar or ischemia on 201T1 images. By segmental myocardial analysis, exact concordance was obtained in 463/570 myocardial segments (81%). This multicenter Phase I and II study indicates that planar [99mTc]HEXAMIBI stress imaging is safe and compares well with 201T1 stress imaging for detection of coronary artery disease.

Prevention of postoperative thromboembolism by dextran 70 or low-dose heparin.

The efficacy of intravenous infusion of dextran 70 or subcutaneous administration of low-dose heparin in preventing postoperative thromboembolic complications has been investigated in a prospective randomized trial. During part 1 of the study, 232 patients over the age of 40 years who were undergoing major gynecologic surgery underwent a complete test protocol. The 125I fibrinogen uptake test (FUT) was used for the diagnosis of deep vein thrombosis (DVT) in 117 patients in the dextran and 115 patients in the heparin group. Heparin was significantly more effective than dextran for reducing DVT (P less than .001). During part 2 of the study no FUT was done but the incidence of clinical and fatal pulmonary embolism (PE) and the number of complications were studied. Of 444 patients (parts 1 and 2) 1 fatal and 2 nonfatal pulmonary emboli were diagnosed. All the emboli occurred in the dextran group. The benefit: hazard ratio appeared to favor heparin for the prophylaxis of DVT.

Some chemical aspects of labeling human fibrinogen with 99m-technetium.

Human fibrinogen was labeled with 99m-Technetium. Tin(II)-chloride in citric acid served as reducing agent for the pertechnetate-ion, eluted from a Mo-Tc-generator. Before adding the fibrinogen, the citric acid was always neutralized with sodium hydrogen carbonate. The influences on the quantity of fibrinogen bound 99m-Tc of the relative concentrations of Sn(II), fibrinogen and sodium hydrogen carbonate, of the reaction time and temperature were tested by thin-layer chromatography. The reaction temperature of 28 degrees C showed an optimum of fibrinogen bound 99m-Tc for the reaction time from 1 and 2 hours. With a reaction time of 30 minutes not enough 99m-Tc was bound to fibrinogen, the doubling of the reaction time from 1 to 2 hours showed only an increase of binding of less than 4%. The concentration of Sn(II) with respect to the fibrinogen concentration showed no influence on the quantity of fibrinogen bound 99m-Tc at low Sn(II)-concentrations. At values higher than 34 times of the fibrinogen concentration a decrease of the quantity of bound 99m-Tc was observed. The concentrations of sodium hydrogen carbonate showed no influence on the quantity of fibrinogen bound 99m-Tc but on the clottability of fibrinogen, the pH of the solution must be approximately 7.5. In 3 parallel and independent experiments under optimized conditions (1 hour at 28 degrees C, molar ratio of Sn(II) : fibrinogen = 8.5, pH = 7.5) 89.97 +/- 0.92 % of 99 m-Tc were bound to fibrinogen. Controls of these results by column chromatography showed a binding of 81.08 +/- 1.47 % of 99m-Tc to fibrinogen. The clottability of fibrinogen tested by the method of Clauss (1) was entirely preserved.

[Acetazolamide stimulation test in the preoperative assessment of cerebrovascular reserve capacity in unilateral carotid obstruction]. / Acetazolamid-Stimulationstest bei präoperativer Evaluation zerebrovaskulärer Kapazitätsreserve bei einseitiger Karotisobstruktion.

Using the 16-detector 133Xe-NaCl technique (Novo Cerebrograph) quantitative measurements of regional cerebral blood flow (rCBF) were performed in 13 patients with unilateral carotid obstruction before and after stimulation with 1 g acetazolamide. In all patients resting studies showed no significant difference in hemispheric perfusion and a 47% flow increase after acetazolamide on the side with normal carotid artery. On the obstructed side in 8 patients the hemispheric flow increased equally indicating a sufficient and adequate intracerebral collateral circulation and capacity. In 5 patients a significant redistribution of brain flow occurred with diminished increase on the occluded side. This flow pattern indicates an inadequate vasodilator response and insufficient collateral capacity. The rCBF stimulation test identifies patients with a restricted collateral capacity and these patients could benefit from a surgical treatment.

[Retention and dosage in radiation synovectomy with yttrium-90-silicate colloid]. / Zur Frage der Retention und der Dosis bei der Radiosynoviorthese mit Yttrium-90-Silikatkolloid.

Investigations on patients and on phantoms were performed to determine the retention and the absorbed dose in radiation synovectomy with 90Y silicate colloid. The electrons of 90Y are totally absorbed within the surrounding tissue and produce bremsstrahlung with a maximum intensity at about 110 keV. After application of 6 mCi 90Y the dose rate of the bremsstrahlung was measured at a distance of 10 cm over 13 knees in a total of 10 patients and was found to range between 0.6 and 1.3 mR/h. During a period of 3 hours up to 3 days after injection practically no removal of the material from the joint was observed. According to approximative calculations the mean dose absorbed in the knee ranged between 3650 and 7300 rad, and the absorbed dose in the synovium between 5500 and 11000 rad.

[In vitro and in vivo diagnosis of borderline hyperthyroidism]. / In vitro- und in vivo-Diagnostik der Grenzhyperthyreose.

The evaluation of "preclinical hyperthyroidism" includes laboratory and in vivo tests. The measurements of circulating total thyroxine (T4) and total triiodothyronine (T3) depend on the plasma concentration of thyroid hormone binding proteins. A simple approach, the calculation of the free T3 index (FT3I) and the augmented FT3I (aFT3I) from total T3 and T3-resin uptake corrects the total serum T3 for variation in thyroid hormone binding capacity. In a group of 95 patients with border-line elevated T3 levels we have correlated the results of FT3I and aFT3I with clinical, biochemical and radioisotope findings. It was shown that in patients with moderate elevation of T3 the FT3I and aFT3I are capable of distinguishing clearly between the euthyroid and hyperthyroid range. To detect an imbalance in the hypothalamic-pituitary-thyroid axis either the T4-suppression test or the TRH-test could be used. In 60 patients with "preclinical hyperthyroidism" we have compared both of them. In 77% of the patients the T4-suppression test and i.v. TRH-test provided concomitant results. In 13 patients without response to the i.v. TRH-test 7 showed a definite (more than 50%) and 6 a partial suppression (10-40%) of radioiodine uptake. This suggests that there is no sharp distinction between hyper- and euthyroidism.

First experiments on radioimmunodetection with b-12-monoclonal antibody fragments against breast cancer antigen.

In 14 patients with breast cancer the results of radioimmunoscintigraphy with 123I-labeled b-12 monoclonal antibody fragments were correct in more than two thirds of the patients.

[Cerebral circulation at rest and following CO2 stimulation in patients with unilateral carotid obstruction]. / Zerebrale Durchblutung in Ruhe und nach CO2-Stimulation bei Patienten mit einseitiger Karotisobstruktion.

Using the 16-detector 133Xe-NaCl-technique (Novo Cerebrograph) quantitative measurements of regional cerebral blood flow (rCBF) were performed in 14 patients with unilateral carotis obstruction before and during stimulation with 3% CO2 inhalation. In all patients resting studies did not show any significant differences in hemispheric perfusion. In 11 patients the hemispheric blood flow increased significantly (by more than 6%) during CO2 inhalation on the side without carotis obstruction. The following results were found after 3% CO2-stimulation over the hemisphere with the obstructed carotid artery: 1) rCBF increased significantly on both sides (n = 6) indicating the sufficiency of cerebral collateral circulation; 2) a side-to-side significant difference (n = 4) with the lower perfusion on the pathological side, indicating a decreased or suspended reserve capacity; and 3) bilateral loss of cerebrovascular reactivity (n = 4) as indicator of insufficiency of cerebral collateral circulation. Asymmetry in rCBF or missing cerebrovascular reserve are indications for surgical treatment of the carotis obstruction.

99Tcm-labelled HSA-nanocolloid versus 111In oxine-labelled granulocytes in detecting skeletal septic process.

Fifty-seven investigations of the skeletal system were performed on 54 patients, using a 99Tcm-labelled nanometer-sized HSA colloid in a crossover comparison with 111In oxine-labelled granulocytes for the detection of sites of infection. The findings were in agreement in 55 out of 57 investigations (96.5%). Based on 44 studies in which a final clinical diagnosis was obtained, both methods were found to display the same specificity (93%), whilst the sensitivity of 99Tcm nanocolloid scintigraphy (87%) was slightly higher than that obtained with 111In leucocyte scintigraphy (81%). In our opinion, 99Tcm nanocolloid is easier to use and the total duration of the investigation is considerably shorter. The use of 99Tcm is scintigraphically more advantageous and, with the dosage required, the absorbed radiation dose to the red bone marrow is three times lower than with 111In granulocytes. For the detection and therapy monitoring of osteomyelitis, as well as for the investigation of arthroplasties suspected of infective loosening, we consider scintigraphy with 99Tcm nanocolloid to be equivalent to leucocyte scintigraphy. Identical findings were obtained with both tracers in suspected spondylodiscitis.

Scintigraphy of inflammation with nanometer-sized colloidal tracers.

The biodistribution of a nanometer-sized colloid was tested in three groups of rats, one with a turpentine-induced abscess and one with a histamine-induced oedema in the musculature of a hind leg. The third group served as a control. A 99Tcm-labelled colloid with a mean particle size of 30 nm was administered to each group intravenously. The biodistribution of the tracer, studied 1 h after injection, demonstrated that the colloid accumulated to a very limited extent in oedematous tissue, whereas the uptake in inflamed muscle was high. The colloid was subsequently administered to patients with arthritis, osteitis and osteomyelitis. All sites of inflammation accumulated the radiopharmaceutical and could be visualized scintigraphically 45 min after its administration. The results were in agreement with 67Ga-citrate or 111In-leukocyte scintigraphy, and/or other diagnostic modalities. Hyperaemia alone was not sufficient to cause uptake. We conclude that the mechanism of uptake is regional spilling of the tracer into the extravascular space through gaps in the damaged basement membrane, and that nanometer-sized 99Tcm-labelled colloid may constitute a convenient radiopharmaceutical for detecting inflammation in the extremities.

Assessment of uteroplacental hemodynamics in complicated pregnancy.

Examination of the uteroplacental hemodynamics was performed on 109 occasions in women admitted to the hospital in the third trimester because of various complications of pregnancy. The radioactive tracer 113m In was injected intravenously and the build-up and equilibrium times were measured over the placenta, myometrium and heart. The placental build-up times were most informative, with prolonged values being recorded in about one quarter of these cases. When those extending beyond three minutes were further studied, they were usually found to be associated with severe complications of pregnancy. This did not obtain in cases with shorter placental build-up times.

Antianginal drug effects on normal, ischemic and scar myocardial segments in man.

In order to assess acute effects of nitroglycerin, nifedipine and metoprolol on normal, ischemic and scar myocardial segments in man, non-invasive hemodynamic and radionuclide measurements of left ventricular function were performed. Sixteen patients with single left anterior descending (LAD) disease were studied at rest and during exercise: 9 patients with angina and exercise-induced ischemia (LAD stenosis) and 7 patients with previous transmural myocardial infarction and no ischemic changes at thallium imaging (LAD occlusion). Effects on regional ejection fraction were compared between involved antero-septal and normal postero-lateral areas. Global ejection fraction at rest was unchanged after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, improvement in exercise ejection fraction after all drugs was due to increased regional ejection fraction in ischemic segments, i.e. a real anti-ischemic effect could be demonstrated. In regions of myocardial scar, regional ejections fraction was not changed after either drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine but decreased after acute beta-blockade. Despite the very similar anti-ischemic effects of all drugs, underlying hemodynamic mechanisms were quite different: Reduction in preload and afterload after nitroglycerin, vasodilatation and reflex sympathetic activity after nifedipine and reduction in double product and contractility after metoprolol. Thus, the mode of action of nitroglycerin, nifedipine and metoprolol on normal, ischemic and scar myocardial segments could be demonstrated in man. Non-invasive antianginal drug testing as shown in this study should allow optimal medical therapy for patients with chronic ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[The action of Buphenin on uteroplacental haemodynamics (author's transl)]. / Effets de la buphénine sur l'hémodynamique utéro-placentaire.

The action of buphenin, a uterine relaxant from the group of adrenergic beta-mimetics, was examined on the blood pools of placenta, myometrium and heart, in 10 pregnant women. The method consisted of an i.v. injection of the radioisotope 113m-Indium and of registering the blood pools by external measurement of the gamma-activity. buphenin caused an increase in placental and myometrial blood pools with a corresponding decrease in cardiac blood pool. These changes were observed in all the cases examined and occurred whether the uterus had previously been inactive or in labour. The changes in blood pool were dependent on the dose of buphenin administered but there was no relationship apparent between the degree of pool changes and severity of pregnancy complication prevailing.