Possible tumor localization of Tc-99m-labeled liposomes: effects of lipid composition, charge, and liposome size.

The possible in vivo distribution of liposomes after they have been directly labeled with Tc-99m has been studied in rats bearing the Walker 256 carcinoma. The importance of lipid composition, charge, and size of liposome were studied with respect to possible tumor-localizing properties. Tumor uptake was best with small, fluid-membrane, negatively charged liposomes, as indicated by the distribution of the Tc-99m label. The uptake was visualized on scintigrams.

Doppler determined aortic acceleration after dipyridamole in the prediction of coronary artery disease.

Change in the acceleration of aortic blood flow with stress testing is reported to reflect the presence of myocardial ischaemia. We studied its clinical usefulness when compared with dipyridamole thallium scintigraphy in 101 patients, of whom 64 had coronary angiography. Maximum aortic acceleration increased after dipyridamole (P < 0.0001), although no correlation existed between the aortic acceleration and evidence of thallium perfusion abnormalities. For the patients who had angiography, the increase in aortic acceleration was similar for those with no significant coronary stenoses, single vessel or multi-vessel disease. Compared with coronary angiography, Doppler measurement of maximum aortic acceleration had a sensitivity of 92% and a specificity of 37% for the detection of coronary artery disease. When patients with previous myocardial infarction or left ventricular dysfunction were excluded, there was still no relationship between the maximum aortic acceleration and the presence of coronary artery disease. We conclude that changes in the acceleration of aortic blood flow after dipyridamole stressing do not predict the presence or severity of coronary artery disease as measured from perfusion defects at thallium scintigraphy or by coronary angiography. We have observed a wide variability of aortic maximum acceleration in the evaluation of myocardial ischaemia, which we feel introduces serious limitations to its use in routine clinical practice.

Staging of prostatic carcinoma with radionuclide bone scintigraphy and lymphography.

One hundred patients with histologically proven carcinoma of the prostate were examined by radionuclide bone scintigraphy and bipedal lymphography. In 27 cases the bone scintigram and lymphogram were positive, in 16 the bone scintigram only was positive and in 10 the lymphogram only was positive. Although radionuclide bone scintigraphy is the most useful single investigation for detecting metastatic spread from prostatic carcinoma, lymphography should be performed if the bone scintigram is negative, as it is likely to demonstrate nodal metastases in 18% of patients.

Safety of intravenous dipyridamole thallium myocardial perfusion imaging: experience in 435 patients.

Dipyridamole stress 201Tl scintigraphy is widely used in the investigation of myocardial ischaemia. We report our experience of adverse effects observed during this diagnostic procedure. A prospective study was undertaken of 435 consecutive patients (mean age 59 years; 273 males) referred to two nuclear medicine departments for assessment of myocardial perfusion was undertaken. Patients were monitored prior to and following the infusion of dipyridamole. All symptomatic, haemodynamic and electrocardiographic changes were documented. No deaths occurred in this series. Adverse events were observed in 174 (40%) patients. Of these, three patients experienced 'major' adverse events (0.6%) requiring hospitalization (myocardial infarction = 1; chest pain = 1; simple partial seizure = 1). 'Moderate' adverse events occurred in 39 (8.9%) patients and required intravenous aminophylline to reverse effects (ST segment abnormalities = 26; nausea = 7 headache = 3; chest pain = 2; bronchospasm = 1; protracted vomiting = 1; diarrhoea = 1). 'Minor' adverse events were experienced by 132 (30.3%) patients and did not require aminophylline. Sixty per cent of our patients experienced no ill effects from dipyridamole given as an exercise substitute in conjunction with 201Tl imaging. The rest had symptoms which were mostly mild, although a few patients found the experience unpleasant. Only one patient experienced a life-threatening episode.

Radioimmunolocalization of tumours by external scintigraphy after administration of 131I antibody to human chorionic gonadotrophin: preliminary communication.

(131)Iodine ((131)I) labelled antibody directed against human chorionic gonadatrophin (hCG) was given on 21 occasions to 18 patients with hCG-producing neoplasms. Tumours were localized by external scintigraphy in 13 of 21 investigations. Positive results were obtained reliably when serum hCG exceeded 500 miu/ml and in some cases sensitivity was comparable to that of computerized tomography. A positive result probably implies viability in the tumour and this was of practical value in discriminating between necrotic deposits and living tumour before surgery.

Case report: deep venous thrombosis diagnosed on indium-111 labelled white cell scanning.

We report a patient with pyrexia in whom deep venous thrombosis was diagnosed incidentally on Indium-111 labelled white cell scanning. The role that white cells play in thrombogenesis is discussed.

Arthritis in scleroderma.

Thirty-four patients (24 females and 10 males) selected from 300 consecutive patients with established systemic sclerosis (SSc), with a current or past history of articular symptoms, were clinically documented and further studied using thermography and bone scan to define the pattern of arthritis. Clinical evidence of synovitis was observed in 30 (88%) and joint inflammation was detected in 31 (91%) by the above-mentioned imaging techniques. A distinctive subset of 10 patients with deforming arthritis was characterized in which seven (70%) patients fulfilled criteria for both rheumatoid arthritis and SSC; three of these satisfied the criteria for diagnosis of CREST, but none met the criteria of mixed connective tissue disease. These patients, as a group, when compared with the rest showed limited skin involvement (skin score of 19 +/- 11 vs 33 +/- 14; P < 0.05) and were positive for rheumatoid factor (80 vs 13%; P < 0.05) and anticentromere antibodies (37 vs 4%; P < 0.05).

Technetium-99-labelled methylene diphosphonate uptake scans in patients with dialysis arthropathy.

Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy.

Contribution of diaschisis to the clinical deficit in human cerebral infarction.

BACKGROUND AND PURPOSE: Regions of decreased cerebral blood flow are often seen on single-photon emission computed tomography (SPECT) after stroke and have been widely reported to add to the clinical deficit. However, such reports have not distinguished between correlation and causation. We analyzed 124 serial SPECT scans performed in 50 patients to assess the role of diaschisis in the clinical deficit after stroke. METHODS: SPECT with the use of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) was performed in a prospective, unselected series of 50 patients with cerebral infarcts studied at a median of 1.1, 6.8, and 95 days after ictus. Patients were also assessed with the use of the Canadian Neurological Scale, the Barthel Index, a neuropsychological evaluation, and infarct volume measurement. RESULTS: One hundred twenty-four serial SPECT scans were done in 50 patients. Diaschisis was identified at 168 sites. There was insufficient correlation between diaschisis and the clinical measurements to support the suggestion that diaschisis independently causes clinical deficits beyond those due to the infarct itself. Unlike the clinical status, diaschisis showed little tendency to resolve during the 3-month follow-up period of the study. Several of the instances of correlation were shown to be of a noncausal kind, with both the diaschisis and the clinical deficit being due to the lesion directly; there was no known mechanism for the diaschisis to cause the clinical deficit. CONCLUSIONS: Diaschisis does not independently add to the clinical deficit after stroke. It is more likely that it simply represents part of the damage done by the stroke.

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients.

The possible use of liposomes (phospholipid vesicles) to direct cytotoxic drugs to tumours has led us to investigate the tissue localization of i.v. injected 99m-Tc-labelled liposomes in cancer patients. Twenty mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine : cholesterol : phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label.

Liposomally entrapped second antibody improves tumour imaging with radiolabelled (first) antitumour antibody.

The usefulness of antibodies directed against tumour products for localisation and therapy of cancer is limited by the large proportion of administered antibody which remains non-specifically in the circulation and extravascular space. Liposomally entrapped second antibody (LESA) directed against the first (antitumour) antibody has been used to accelerate clearance of non-tumour-bound first antibody without affecting its clearance from the tumour. Intravenously administered LESA binds the first antibody and LESA is cleared by the reticuloendothelial system. LESA accelerated clearance of radiolabelled antibody directed against carcinoembryonic antigen (CEA) from the circulation in four of five patients with gastrointestinal cancer, enhancing gamma-camera imaging of the tumour in three of them. These results suggest that LESA can improve the sensitivity and specificity of tumour imaging with radiolabelled antitumour antibody. This strategy may also have the potential to improve the therapeutic ratio of some toxic agents linked to antitumour antibody.