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An evaluation of methods for sizing radiocolloidal particles.

Technetium-99m-labelled colloids covering the entire spectrum of particle size were prepared from commercial kits (antimony colloid, sulphur colloid, tin colloid) or by chemical (excess aluminium) or thermal modification of sulphur colloid (heating time of 30 min). Particle size measurements were obtained using electron microscopy and/or a laser light scattering technique. The results for antimony colloid agreed reasonably well for both techniques with a range of 3 to 25 nm. However, standard sulphur colloid had a smaller size (220 nm) when measured by electron microscopy in comparison to the larger size (390 nm) obtained with the light scattering method. This discrepancy was felt to be due to artefacts created by electron microscopy. These artefacts (drying and sublimation) were avoided by the laser light scattering techniques which has the advantage of being non-destructive and of quickly sizing particles while still in solution. The larger colloidal particles were sulphur colloid doped with aluminium ions (1000 nm) and the tin colloid (2500 nm) which were sized by electron microscopy and laser light scattering respectively.

Antimony↗

Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging.

BACKGROUND AND AIM: Various mannose receptor-binding agents, for example 99mTc-diethylenetriaminepentaacetic acid (DTPA)-mannosyl-polymer, have been developed for sentinel lymph node (SLN) imaging. In order to simplify the synthesis and labelling procedure and to improve the biological properties, we developed a novel mannose receptor-binding agent, 99mTc-neomannosyl human serum albumin (99mTc-MSA), for SLN imaging. METHODS: MSA was synthesized by conjugating mannopyranosylphenylisothiocyanate to human serum albumin (HSA). After reducing MSA with beta-mercaptoethanol and PD-10 column purification, a medronate solution containing stannous fluoride was added, divided into aliquots and freeze-dried. Reduced MSA was labelled with 99mTc-pertechnetate solution. The stability was checked for 24 h at 37 degrees C in human serum. The biodistribution of 99mTc-MSA in mice was investigated by intravenous injection through the tail vein and subcutaneous injection into the foot pad. The biodistributions of 99mTc-HSA and 99mTc-antimony sulphur colloid (99mTc-ASC) were also investigated for comparison. Dynamic whole-body images were obtained for 30 min after subcutaneous injection into the rats' foot pads. RESULTS: The number of mannose molecules conjugated per MSA was 15.9. The number of thiol groups produced was 19.4 per MSA after reduction with beta-mercaptoethanol. Labelling yields were always higher than 97%. 99mTc-MSA was stable for 24 h at 37 degrees C in human serum. The biodistribution in mice after intravenous injection showed high liver uptake (50.7+/-5.5% and 42.7+/-3.7% injected dose per gram at 10 and 60 min, respectively). 99mTc-MSA and 99mTc-ASC showed high accumulation in the lymph nodes after subcutaneous injection, whereas 99mTc-HSA and Tc-tin colloid did not, in both biodistribution and imaging studies. CONCLUSIONS: We have successfully developed a novel 99mTc-MSA for lymphoscintigraphy. The results of animal studies show that 99mTc-MSA has promising properties for SLN imaging.

Animals↗

Determination of filtration fraction using the gamma scintillation camera.

A simple technique for determining effective renal plasma flow, filtration fraction and filtration rate is described. The determination depends upon the use of 131iodine labeled hippuran and 99mtechnetium labeled iron ascorbate or Sn diethylenetriaminepentaacetic acid. The filtration fraction is determined by dividing the corrected uptake for the technetium compound by the corrected uptake for radiohippuran. The uptake is simply determined by the 1 to 2-minute count over the kidneys with background subtraction and taking into account the amount injected. The technique is simple, quick and appears to be a useful clinical tool.

Female↗

Rationale and radiopharmaceuticals for myocardial imaging.

Static radionuclide imaging procedures are now available for evaluating regional myocardial perfusion and for detecting acute myocardial infarction. Thallium-201, a radiopharmaceutical that possesses many of the characteristics of potassium analogues, at present is receiving the greatest attention as a regional blood flow indicator. Ischemic lesions appear as areas of decreased tracer uptake. Unfortunately, this agent is expensive, is in limited supply, and has a photopeak that is low for optimum imaging. Positive infarct images can be obtained with various Technetium-99m chelates. Pyrophosphate appears to be the best of the technetium compounds studied to date, although the mechanism of uptake of the chelates has not yet been fully elucidated. Therefore, quantitative measurements of infract size are not justified. As perfusion imaging and infarct imaging provide useful, complementary data, a dual tracer approach to evaluating patients with suspected coronary artery disease and/or myocardial infarction, is probably justifiable.

Ammonia↗

Usefulness of myocardial perfusion SPECT in patients with left bundle branch block and previous myocardial infarction.

BACKGROUND: The diagnostic value of myocardial perfusion scintigraphy in patients with left bundle branch block (LBBB) and previous acute myocardial infarction has not been evaluated. OBJECTIVE: To determine the utility of single photon emission computed tomography (SPECT) in patients with LBBB and previous acute myocardial infarction. METHODS: Seventy two consecutive patients with permanent LBBB and previous acute myocardial infarction were studied with stress-rest SPECT using 99mTc compounds. The same stress procedures were followed in all patients: (1) exercise alone when it was sufficient; (2) exercise plus simultaneous administration of dipyridamole if exercise was insufficient. RESULTS: In 26 of 28 patients (93%) who had a Q wave acute myocardial infarct before the development of LBBB, there was concordance between abnormal Q waves and rest SPECT in the localisation of myocardial necrosis (kappa = 0.836; p = 0.0001). In 48 patients who had coronary angiography, the positive predictive value of exercise (+dipyridamole) myocardial SPECT for the diagnosis of left anterior descending coronary artery stenosis was 93%, for left circumflex coronary artery stenosis, 96%, and for right coronary artery stenosis, 89%. Specificity values were 83%, 91%, and 69%, respectively. However, sensitivity (69%, 64%, and 89%) and negative predictive values (48%, 46%, and 82%) were suboptimal. CONCLUSIONS: Rest myocardial perfusion SPECT with technetium compounds is useful for localising healed myocardial infarction in patients with LBBB, and exercise (+dipyridamole) SPECT has a high positive predictive value and specificity for the diagnosis of coronary stenosis in these patients.

Aged↗

Carcinoma of the prostate: a critical look at staging.

To stage accurately the extent of the disease comprehensive investigations were done on 75 patients with histologically documented carcinoma of the prostate. Estimation of bone marrow acid phosphatase appears to be the most sensitive test to detect blood-borne metastases. Serum acid phosphatase appears to be of little value in the detection of early blood spread and may have a role only in monitoring the effect of treatment on advanced disease. Bone scanning with technetium compounds has the disadvantage of non-specificity but has far greater sensitivity than a skeletal survey. Bone marrow cytology was not rewarding in the detection of early metastatic disease. Pedal lymphangiography is a highly inaccurate method to detect lymphatic spread of carcinoma of the prostate and pelvic lymphadenectomy, when indicated, remains the only truly adequate method to assess lymph node involvement. There was a 37 per cent incidence of metastatic lymph node pathology in 30 patients undergoing this procedure before either radical prostatectomy or deep x-ray therapy. A close correlation was found between stage and grade of disease and incidence of nodal pathology. There was some correlation between degree of nodal involvement and evidence of blood spread as detected by elevated bone marrow acid phosphatase levels. The significance of this finding remains unclear.

Acid Phosphatase↗

Preoperative cutaneous lymphoscintigraphy in malignant melanoma.

To identify the regional lymph node basins cutaneous lymphoscintigraphy with technetium 99m rhenium sulfide colloid (99mTc-ReS) was performed in 45 patients and with technetium 99m antimony sulfide colloid (99mTc-Sb2S3) in seven patients after excisional biopsy of the primary tumor. All patients had skin tumors located in the face or neck or on the trunk with 47 cases of cutaneous malignant melanoma and 5 cases of benign or premalignant lesions. In 48 patients the scintiscans 1 hour after perilesional injection of the tracer colloid clearly showed the lymphatic drainage patterns from the tumor sites, of them 25 patients demonstrated unidirectional drainage, whereas the remaining 23 patients had multidirectional drainage to two or three lymph node groups. There were technical difficulties in performing the examinations in four patients. The authors recommend cutaneous lymphoscintigraphy as a safe, simple and reliable technique for mapping the lymphatic drainage preoperatively in patients with Stage I cutaneous malignant melanoma of axial localization.

Adult↗

Technetium-99m radiochemical assay by rapid filtration: a superior alternative to chromatography.

A new method for simultaneously measuring radiochemical purity and estimated lung trapping of colloidal technetium-99m (99mTc) radiopharmaceuticals is described. The method employs a small filtration device comprised of two stacked membrane filters, differing in membrane composition and in pore size, situated over a filtrate collection vial. Specifically, an 8-microns pore polycarbonate membrane filter is situated above a 0.22-microns pore mixed-cellulose-esters membrane filter. For assay, a diluted aliquot of radiopharmaceutical is passed through the filtration device. Technetium-99m radioactivity on the membranes and in the vial is then measured. The polycarbonate filter traps and quantitates lung-capillary-occluding particles. The mixed-cellulose-esters filter traps and quantitates radiocolloid particles irrespective of relative size. The filtrate contains free pertechnetate. Within 4 min, this method yields results that compare well with those achieved by conventional techniques. The method works equally well for large colloidal particles [( 99mTc]stannous colloid), intermediate-size particles [( 99mTc]sulfur colloid), and small-size particles [( 99mTc] antimony trisulfide colloid).

Antimony↗

Detection of malignant soft tissue tumors in bone imaging.

A total of 2530 consecutive bone scans were examined to evaluate the number and the type of soft tissue neoplasms detected with bone-seeking phosphonates. Sixty-eight primary or secondary soft tissue neoplasms of 63 patients accumulated 99mTc -methylene diphosphonate and 2 accumulated 99mTc -diphosphonate, and one metastasis was seen as a nonactive 'cold' focus in the urinary bladder. The localization of tumors was: 19 in the lung, 15 in the liver, 11 in the kidney, 10 in the peritoneal cavity or ascites, 5 in the large bowel, 4 in the vascular or lymphatic system, 3 in the connective tissue or muscles, 2 in the ovary, 1 in the urinary bladder, and 1 in the brain. Our results differ in many respects from those reported in the literature. The causes of the differences are discussed.

Abdominal Neoplasms↗

Deposition of small 99mTc-labelled colloids in bone marrow and lymph nodes.

The degree of deposition of small-particle colloids such as 99mTc-antimony sulfide colloids (ASC-group) and 99mTc-rhenium colloid (Tc-Re) in the bone marrow and lymph node was studied. H-ASC that was prepared in our laboratory was concentrated to a higher degree both in the bone marrow and lymph nodes, compared with other colloids. The H-ASC were mostly from 5 to 12.5 nm and the shape was uniform and spherical. The degree of deposition of Tc-Re in rabbit lymph nodes was not higher, however, the label was considered to be valuable clinically. The degree of deposition of Tc-Re in the bone marrow was not satisfactory. The size of Tc-Re was much smaller than H-ASC, ranging from 3 to 5 nm. From these results, it is considered that factors affecting deposition in the marrow are not identical to those in the lymph nodes.

Animals↗

A simple radio-isotopic method for the detection of bronchial inhalation during intensive care.

The high incidence of pneumopathy in intensive care units might be due to the pulmonary aspiration of gastric juice following gastro-oesophageal reflux. The paper describes a radio-isotopic method using material easy to install at the patient's bedside. This technique demonstrated aspiration of gastric juice in the lungs of 8 of 25 intensive care patients investigated. Such a method might be useful later to demonstrate that silent bronchial aspirations of gastric juice are responsible for pulmonary complications.

Humans↗

Radiology of giant cell tumors of bone: computed tomography, arthro-tomography, and scintigraphy.

Radiologic studies of 50 giant cell tumors of bone in 48 patients were useful in assessing the anatomic extent for planning surgical treatment. Contrast-enhanced computed tomography (CT) provided the most useful and complete evaluation, including soft tissue extent and relationship to major vessels. Angiography was useful when the extraosseous extent and vascular relationships were not entirely clear on CT. Arthro-tomography was the best way to evaluate tumor invasion through subchondral cortex and articular cartilage. Reactive soft tissues, with edema and hyperemia, were difficult to distinguish from tumor tissue on CT and angiograms. Bone scintigrams often showed intense uptake beyond the true tumor limits.

Adolescent↗

Radionuclide imaging in histiocytosis X.

Radionuclide imaging (99mTc bone scans, 99mTc S colloid scans, 99mTc brain scans and 67gallium scans) and bone radiographs were done in 54 children with histiocytosis X. The results are discussed, compared with the literature and indications for the different nuclear medicine studies are given.

Adolescent↗

Uterine doughnut in early proliferating phase: potential pitfall in gastrointestinal bleeding studies.

A 41-year-old woman with rectal bleeding was referred to our department for gastrointestinal (GI) bleeding study. She was in early post-menstrual period and had stable vital signs. A GI bleeding study with Tc-99m SC revealed uterine blush in the pelvis. The shape of activity and quick fading excluded a GI bleeding. To rule out an intermittent bleeding, patient underwent a second bleeding study with Tc-99m RBC. Serial images showed uterine "doughnut" in the pelvis. The activity neither changed in shape nor showed distal movement with time excluding a GI hemorrhage. Uterus in early proliferating phase could be a potential pitfall in GI bleeding studies.

Diagnosis, Differential↗

Radiolabeled antibodies, albumin and antimony sulfide colloid: a comparison as lymphoscintigraphic agents.

The kinetics of lymph node and systemic uptake of members of three different classes of lymphoscintigraphic agents were studied in normal laboratory rats. 99mTc antimony trisulfide colloid (TcSbC), 99mTc human serum albumin (TcHSA), 125I 5G6.4 (a murine IgG2ak monoclonal antibody), 125I 763.24T (a murine IgG1), and 125I FT166 ( a murine IgM monoclonal) all current or potential lymphoscintigraphic agents, were injected subcutaneously into the hind foot pads of healthy rats. Ipsilateral and contralateral popliteal lymph nodes were sampled up to 4 h post-injection. Subcutaneous injection resulted in far higher nodal uptake for all agents than i.v. delivery with ipsilateral popliteal node/blood ratios 1 h postsubcutaneous injection of: for TcSbC (1900) greater than 125I IgM (497) greater than TcHSA (72) greater than 125I Intact IgG2a or 125I IgG1 at approximately 10. Thus, while all agents achieve popliteal node/blood ratios far greater than unity, TcSbc has the greatest absolute and relative nodal accumulation, greater than the 125I IgM monoclonal antibody and TcHSA. Uptake of the intact 125I IgG antibodies is lowest. These data suggest that TcSbC in particular, as well as TcHSA and IgM may be most useful as non-specific nodel imaging agents, while the lower background activity of the IgGs may make targeting specific antigen in nodes more feasible.

Animals↗

Immunoscintigraphy of melanoma using radiolabelled antibodies: pilot, prospective studies and Italian multicenter clinical trials.

The studies on radioimmunodetection of malignant melanoma reported are based on the use of the 225.28S monoclonal antibody against a high molecular weight melanoma associated antigen, an IgG2a isolated and characterized by Ferrone et al. The strategy followed by us to check the characteristics and the behaviour of this antibody and to verify its possible use in clinical praxis, includes three groups of trials performed from 1982 to 1987. A pilot study was performed on 42 patients with 74 melanoma lesions, a multicenter study was realized, with the collaboration of 10 Italian nuclear medicine centers, on 254 patients with 539 lesions and prospective study performed on 44 patients with 54 suspected regional lymph nodes involvements. High sensitivity and specificity were obtained especially with the use of technetium compound which also allowed the attainment of very high predictive values of positive tests. No adverse reactions were noticed.

Antibodies, Monoclonal↗