Comparison of chemotaxis and superoxide generation of indium-111-oxine- and technetium-99m-HMPAO-labelled granulocytes.

The diagnostic value of imaging infection with labelled granulocytes depends on the functional integrity of the reinfused cells. The aim of this study was to compare the functional integrity of granulocytes labelled with indium-111-oxine and technetium-99m-hexamethylpropyleneamineoxime (HMPAO), respectively, in comparison to unlabelled control granulocytes. Granulocytes were purified from healthy subjects and labelled with either 111In-oxine or 99mTc-HMPAO. Chemotaxis and superoxide production induced by formyl-peptide and phorbol-myristate-acetate were measured. Granulocytes labelled with 111In-oxine had significantly (p < 0.001) decreased chemotaxis. Superoxide production of granulocytes stimulated with phorbol-myristate-acetate showed no significant difference between control cells and those labelled using either technique. In contrast, formyl-peptide-stimulated superoxide production was increased in granulocytes labelled with 111In-oxine (p < 0.01) and in cells labelled with 99mTc-HMPAO (p < 0.03), indicating a priming compared to unlabelled cells. In conclusion, 99mTc-HMPAO-labelled granulocytes show biological properties superior to 111In-oxine-labelled cells, and should therefore be favoured for use in leucocyte labelling and infectious disease imaging.

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.

Prevention of deep vein thrombosis in patients with hip fractures: low molecular weight heparin versus dextran.

A randomized open trial was undertaken to compare the antithrombotic efficacy of a low molecular weight heparin (LMWH; Sandoparin) with that of dextran 70 in patients undergoing surgery for hip fracture. One hundred thirteen patients received LMWH once daily subcutaneously at a fixed dosage while 103 patients received intravenous dextran 70. Postoperative deep vein thrombosis (DVT) was assessed by a diagnostic algorithm using the 125Iodine fibrinogen uptake test as screening and Duplex ultrasonography and/or ascending venography as confirming techniques for suspected DVT. The frequency of DVT was significantly lower in the LMWH group than in the dextran group (15.5 versus 32.6%, p less than 0.005). Proximal DVT was rare in both groups (LMWH: 2%, Dextran: 1%). Only one case of fatal fat pulmonary embolism was observed during the 10 day prophylaxis period in a patient receiving Dextran. Three cases of pulmonary embolism occurred later; one fatal event in the dextran group on day 14, and two cases in the LMWH group (one fatal and one non-fatal event) on day 14 and 17, respectively. There was no major bleeding complication in either group. We conclude that the LMWH we used is safe, was well tolerated, and has a significantly better thromboprophylactic effect than dextran 70.

[Prevention of thromboembolism in hip traumatology: low molecular weight heparin versus dextran]. / Thromboembolieprophylaxe in der Hüfttraumatologie: niedermolekulares Heparin versus Dextran.

A prospective, randomized trial has been undertaken to evaluate the prophylactic effects of low molecular weight heparin (LMWH) and dextran-70 in 216 patients with hip fracture during a postoperative period of ten days. Deep vein thrombosis (DVT) was diagnosed using the 125Iodine fibrinogen uptake test, confirmed by ascending venography. 113 patients received LMWH and 103 dextran-70. The frequency of DTV of 14.2% in the LMWH group was significantly lower compared with the 30.1% in the dextran group (p less than 0.003). During the first 10 days postoperative there were no fatal pulmonary embolism (PE). After this period PE occurred in 2 patients (1.8%) in the LMWH group and 1 patient (1.0%) in the dextran group. In each group one patient died from PE. There was no major bleeding in either group. The frequency of local complications was slightly higher in the dextran group (10.7%) compared with the LMWH group (3.5%). The postoperative hemoglobin level was significantly lower in dextran treated patients than in patients receiving LMWH (p less than 0.0001).

[Risk assessment in diagnostic radiation dosimetry]. / Zur Problematik der Risikobewertung von diagnostischen Strahlendosen.

Regulation of radiological protection in diagnostic radiology is based primarily on theoretical assumptions and hypotheses rather than on quantitative data regarding harmful effects. Bionegative effects of low doses have not been demonstrated in individuals or by epidemiological data. Nonetheless, in every case involving radiodiagnostic or nuclear medicine procedures, a benefit-versus-risk analysis is necessary. Therefore, knowledge of both radiobiological aspects and all the above assumptions, hypotheses and simplifications are necessary in order to optimize radiological protection in diagnostic radiology.

Antibody labeling with copper-67 using the bifunctional macrocycle 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid.

The high kinetic stability of the Cu2+ complex of the chelator 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl]benzoic acid was demonstrated at physiological pH as well as under acidic conditions. The chelating agent was conjugated to AB35, a monoclonal antibody directed against CEA, without a significant loss of immunoreactivity. The conjugate could, under optimal labeling conditions, be labeled with 67Cu in acetate buffer with a full occupancy of ligands within 20 min. This radiolabeled conjugate showed no transfer of radiocopper to serum proteins in human serum over 7 days. The biodistribution in tumor-bearing mice was measured and compared to that of iodinated AB35. Tumor uptake was high with 15 +/- 3% ID (injected dose)/g after 24 h and 32 +/- 7% ID/g after 96 h for the 67Cu-labeled antibody and 13 +/- 4% ID/g after 24 h and 14 +/- 2% ID/g after 96 h for the 125I-labeled antibody. Whereas radioactivity in normal organs decreased with time after 24 h, increased residence time was shown up to 4 days with the 67Cu-labeled AB35.

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.

European multi-centre comparison of thallium 201 and technetium 99m methoxyisobutylisonitrile in ischaemic heart disease.

Fifty-six patients in Europe were entered into a multi-centre study to compare the accuracy of technetium 99m methoxyisobutylisonitrile (99mTc-MIBI) for the detection of coronary artery disease (CAD) with thallium 201 (201Tl) chloride perfusion scanning. The results showed a high degree of concordance between the two radiopharmaceuticals. Some 81% (678/840) of myocardial segments showed the same result (normal, infarct or ischaemia), and 80% (45/56) of patients had the same diagnosis. Overall detection of CAD in patients was 98% for 201T1 and 96% for 99mTc-MIBI. Detection of CAD in total arteries was 68% for both agents. In this study 99mTc-MIBI was as accurate as 201Tl for the detection of coronary artery stenoses.

[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.

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.

[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.

[Nuclear medicine: current aspects and future]. / Nuklearmedizin: Gegenwart und Zukunft.

A survey of the range and progress of nuclear medicine procedures is presented and the accuracy of the modalities is described. The priority in nuclear medicine diagnosis has shifted from proof of the non-functioning nodule to localization of biochemical lesions with the aid of new bioindicators and single photon and positron emission computer tomography. Diagnosis has extended to subcellular regions with the introduction of immunoscintigraphy as well as enzyme and receptor scintigraphy. This is a new dimension to which Swiss nuclear medicine specialists have contributed a great deal.

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.

[Differential diagnosis of pneumonia and pulmonary infarct based on lung scintigraphy]. / Differentialdiagnose von Pneumonie und Lungeninfarkt mit Hilfe der Lungenszintigraphie.

The etiology of radiologic signs of circumscript parenchymatous lesions is multivarious. In some instances infarction of the lung has to be distinguished from pneumonia. The differential diagnosis has important therapeutic consequences for the patient. An important criterion for primary pneumonic infiltration is Xe-trapping within the area lacking perfusion, which can only be demonstrated by perfusion scintigraphy with Xe-133-NaCl. However, infarction of the lung lacks this pathologic feature. Pathophysiologically the various changes may occur as the result of obstruction of the vessel i.e. due to alveolar hypoxia and embolism. In order to improve the diagnostic methods a combination of perfusion scintigraphy using Xe-133-NaCl and Tc-99-macroaggregate and ventilation scintigraphy with Xe-127 was employed. We retrospectively evaluated 20 patients with the nuclear medical diagnosis of either pneumonia (n = 10) or infarction of the lung (n = 10). The following criteria were adopted: history, risk factors, X-ray of the chest, blood chemistry, ECG, phlebography, pulmonary angiography and histopathological diagnosis, as well as the course of the disease. According to our results the specificity of the scintigraphic diagnosis of pneumonia and infarction of the lung was 90%. However these results will have to be verified in a prospective study using pulmonary angiography as the reference method.

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.

Thallium-201 myocardial scintigraphy in coronary triple-vessel disease: an attempt to increase sensitivity using quantitative methods.

In order to increase the sensitivity of thallium-201 exercise scintigraphy in patients with triple vessel coronary disease (TVD), we first examined retrospectively myocardial scintigrams of 179 patients with TVD, as documented subsequently by cardiac catheterization. Ischemia had been diagnosed visually in 141 (79%), scar without ischemia in 25 (14%) and no apparent perfusion defect in 13 (7%) cases. The subset of TVD patients without scintigraphic ischemia (i.e. those with scar or no perfusion defect) was then compared to a control group with normal coronary angiography using four quantitative criteria: (1) in preset-count analog images, a quotient of the exposure times rest image/stress image; (2) in preset-time digital images, a quotient of counts/pixel in stress image/rest image using two different myocardial regions of interest (ROI); (3) a similar quotient using paracardial lung ROIs of three different sizes; (4) the absolute values of stress lung uptake. Quotients (1) and (2) were expected to be lower in TVD patients than in normal controls due to exercise-induced global ischemia, quotient (3) and value (4) were expected to be higher due to exercise-induced left ventricular dysfunction with increased lung uptake of thallium-201. All results showed a tendency to confirm these hypotheses; significant differences (P less than 0.05) between patients and controls were obtained in all lung quotients and in 3 of 12 myocardial quotients. No significant differences were observed in the exposure time quotients of preset-count images and in the stress lung uptake. Due to overlapping values, it was not possible to fix normal and pathological ranges of any quotient.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Evaluation of scintigraphic procedures for clarifying pain conditions in hip joint prostheses]. / Evaluierung szintigraphischer Verfahren zur Klärung von Schmerzzuständen bei Hüftgelenkprothesen.

59 patients with implanted one- or two-sided hip prostheses (n = 74) have been investigated by two different scanning techniques to detect both possible loosening of the prostheses and a possible infection as the cause of the loosening. Of the investigated prostheses 47 were loose; in 45 cases this was evidenced by the bone scan using Tc-99m-DPD, thus showing a sensitivity of 95%. Specificity was 89%. In 21 cases (45%) of loose prostheses an infection could be clinically proven. With the aid of In-111 labeled leukocyte scans, 17 of 21 cases were correctly diagnosed as infected, showing a sensitivity of 91%, while the specificity was 94%. In view of the 93% accuracy, bone scanning can be regarded as the method of choice in detecting loosening of prostheses. The 91% accuracy in proving or ruling out infection by means of the leukocyte scan is high enough to assert correct findings in most cases. The main disadvantage of this method is the very demanding technique for marking of white blood cells.

Extremity bone tumors: evaluation by P-31 MR spectroscopy.

High-resolution P-31 MR spectra were obtained in four patients with bone tumors of their distal extremities. In one case the tumor, a Ewing sarcoma of the tibia, was investigated during clinical remission after radiation therapy and chemotherapy. The other three cases - one low-grade chondrosarcoma of the tibial head, one malignant fibrous histiocytoma of the tibia, and one chondroblastoma of the medial femoral condyle - showed clinically active tumor growth, with corresponding increased metabolism as demonstrated by bone scintigraphy. The spectra of the three active tumors indicated a comparably high adenosine triphosphate content, similar to previously published spectra from animal tumors or human tumors implanted into animals. There were also high resonances of inorganic phosphate and low resonances of phosphocreatine; there were definite peaks in the phosphodiester and phosphomonoester regions, indicating the existence of these metabolites in the tumors. Slight but definite changes in the metabolite content were observed in one tumor after chemotherapy. The spectra of the unaffected leg did not show any well-resolved P-31 signals, which is typical for healthy bone. These are the first P-31 MR spectra of human bone tumors measured in patients to our knowledge.