Disposition of 14C-labelled ENDOTELON in humans.

In order to study the disposition of ENDOTELON in humans, this compound was labelled with 14C by photosynthesis. ENDOTELON consists of a complex of procyanidolic oligomers extracted from the seeds of a variety of vine cultivated in the Bordeaux wine-growing region, and is prescribed for the treatment of chronic venous insufficiency and retinal lesions. Considering the difficulty in labelling the various constituents of the product, the labelling procedure was based on providing radioactive CO2 to the plant. After isolation and purification, 150 mg of active material (50 microCi) was administered orally to six healthy volunteers. Radioactivity was measured in the blood over time until 72 and 120 hours in the same subjects after drug administration. Urinary and faecal elimination was measured for a period of 167 hours. Urinary elimination of the radioactive compounds represented 12 to 27% of the administered dose and faecal elimination represented 47 to 75% depending on the subject. The radioactivity of the 14CO2 eliminated in the breath was also measured, and represented around 8% of the total radioactivity for the 72-hour period after administration. Although the disposition of ENDOTELON is based on the total radioactivity measured over time, this technique allows the evaluation of the elimination rate of the product and its metabolites from the human body.

Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma.

A radiolabeled monoclonal antibody (MAb) that has been shown to react specifically in vitro and ex vivo to human colorectal carcinoma and to inhibit growth of human carcinomas grafted in nude mice was administered to 52 colorectal carcinoma patients and 15 patients with other types of cancer. Of 63 colorectal carcinoma tumor sites studied, 34 showed significant accumulation of antibody by external photoscanning and tomoscintigraphy, whereas none of the 20 sites of other cancer types gave positive results. One-third of the patients received F(ab')2 fragments of the MAb, which gave a slightly higher percentage (61%) of positive results than did intact MAbs (51%). A few patients scheduled for tumor resection were given injections simultaneously of 131I-labeled MAb and 125I-labeled normal immunoglobulin G. Antibody concentration in resected tumors was 3.6 to 6.3 times higher than the average antibody concentration in adjacent normal tissues (1.5, 3.4, and 9.4 as compared with normal mucosa, serosa, and fat, respectively), and the specificity indices, calculated by differential radioactivity analysis, ranged from 2.1 to 5.1. The results show the potential value and limitations of this particular MAb for tumor detection by immunoscintigraphy.

[Diagnosis of internal abscesses by scintigraphy: results of a method using purified granulocytes]. / Diagnostic des abcès internes par scintigraphie: résultats d'une méthode utilisant des granulocytes purifiés.

In the 111-indium-leukocyte scan method described by M. L. THAKUR et al. in 1977 for the diagnosis of abdominal abscesses the whole leukocyte fraction from a blood sample is labeled and injected into patients. We propose a modification in which purified granulocytes are used. The results of 43 granulocyte scans show that this modification does not diminish the sensitivity of the method. Furthermore, it allows the detection of abscesses in a shorter time (2-4 hours after injection) and with 111-indium doses (200 muCi) at least 3 times lower than in the original method. Increased specificity can also be expected.

Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy.

Paul Ehrlich's inspired concept of 'magic bullets' for the cure of diseases has been revitalized by recent advances in immunology(1). In particular, the development of cell fusion technology allowing the production of monoclonal antibodies (Mabs) with exquisite specificities(2) triggered new hopes that we may now have the perfect carrier molecules with which to deliver cytotoxic drugs(3) or toxins(4) to the hidden cancer cells. This article reviews data on one aspect of the magic bullet concept, the use of radiolabelled antibodies as tracers for tumour localization. It will also discuss the very recent clinical use of (131)I-labelled Mabs against carcinoembryonic antigen (CEA)(5) to detect carcinoma either by conventional external photoscanning or by single photon emission computerized tomography (SPELT). This alliance of the most modern tools from immunology (Mabs) and nuclear medicine (SPELT) appears promising as a way to improve the sensitivity of 'immunoscintigraphy'. However, this approach is not yet ready, for widespread clinical use.

[Regional myocardial perfusion in coronary stenosis of varying degrees]. / Perfusion myocardique régionale dans les sténoses coronaires de divers degrés.

Stenoses of the left anterior descending coronary artery of varying severity (15-73% of internal diameter, 20-95% of internal surface) were created in 25 open-chest pigs. The regional distribution of myocardial blood flow perfusion was studied by the radioactive microspheres technique at rest and during reactive hyperemia. Reactive hyperemic responses to 10 sec occlusions were used to produce maximal flow increases and to judge the physiological significance of the narrowings in the subendocardial and subepicardial layers in calculating coronary flow reserves. Measurements of coronary reserve are sensitive indices of functional impairment even when resting flow is unimpaired. At 75% stenosis the subendocardial coronary reserve is completely abolished and the zone perfused by the stenosed artery is unable to increase its flow when needed if the experimental conditions do not change. Any further increase in oxygen demand will provoke electrical and metabolic disorders. For abolition of the subepicardial coronary reserve a 94% stenosis is required.

Use of limitations of radiolabeled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas.

Fifty-three patients with histologically proven carcinoma were injected with highly purified [131I]-labeled goat antibodies or fragments of antibodies against carcinoembryonic antigen (CEA). Each patient was tested by external photoscanning 4, 24, 36 and 48 h after injection. In 22 patients (16 of 38 injected with intact antibodies, 5 of 13 with F(ab')2 fragments and 1 of 2 with Fab' fragments), an increased concentration of 131I radioactivity corresponding to the previously known tumor location was detected by photoscanning 36-48 h after injection. Blood pool and secreted radioactivity was determined in all patients by injecting 15 min before scanning, [99mTc]-labeled normal serum albumin and free 99mTc04-. The computerized subtraction of 99mTc from 131I radioactivity enhanced the definition of tumor localization in the 22 positive patients. However, in spite of the computerized subtraction, interpretation of the scans remained doubtful for 12 patients and was entirely negative for 19 additional patients. In order to provide a more objective evaluation for the specificity of the tumor localization of antibodies, 14 patients scheduled for tumor resection were injected simultaneously with [131I]-labeled antibodies or fragments and with [125I]-labeled normal goat IgG or fragments. After surgery, the radioactivity of the two isotopes present either in tumor or adjacent normal tissues was measured in a dual channel scintillation counter. The results showed that the antibodies or their fragments were 2-4 times more concentrated in the tumor than in the normal tissues. In addition, it was shown that the injected antibodies formed immune complexes with circulating CEA and that the amount of immune complexes detectable in serum was roughly proportional to the level of circulating CEA.

[Use of strontium-89 in the analgesic treatment of bone metastases]. / Emploi du strontium-89 dans le traitement antalgique des métastases osseuses.

The analgesic properties of 89Sr were investigated in 17 patients with multiple painful bone metastases. 89Sr is a radioisotope, the metabolism of which in the body is comparable to that of calcium. It is a pure beta emitter and its half-life is 51 days. When injected intravenously it is captured by bone, especially at locations where the turnover is increased. Each patient received 1--2 mCi of 89Sr. Bone scans and hematological investigations were performed before, and 2 months after, treatment. No significant changes were found. Shealy's method was used to assess pain, initially twice a week and then at more prolonged intervals. One patient suffering from multiple myeloma showed a spectacular improvement and 6 others responded favourably. Improvement generally occurred within 3--7 days, but was sometimes delayed for up to 3 weeks. Relief lasted for up to several months. Five patients had an increase of pain during the 24 hours immediately after treatment. An average of 28% of the administered radioactive dose was found in the urine collections during the first 48 hours. Although the treatment was not successful in every case, the use of 89Sr as a long acting analgesic in multiple bone metastases should be considered more frequently, especially as there are no side effects.

Tumor localization of radio-labeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation.

Purified, [131I]-labeled goat antibodies against carcinoembryonic antigen, which have been shown to localize in human carcinoma in nude mice, were injected into 27 patients with carcinoma. Patients were scanned with a scintillation camera at various intervals. In 11 patients, radioactivity was detectable in the tumor 48 hours after injection. Computerized subtraction of blood-pool radioactivity provided clearer pictures in positive cases, but in 16 patients the scans remained doubtful or negative. To study the specificity of [131I]-antibody localization, we gave some patients simultaneous injections of [125I]-labeled normal IgG. Both isotopes were measured by means of scintillation counting in tumors and normal tissues recovered after surgery. The results demonstrated that only the anti-CEA antibodies localized in tumors. However, the total antibody-derived radioactivity in the tumor was only about 0.001 of the injected dose. We conclude that, despite the present demonstration of specificity, this method of tumor detection is not yet clinically useful.

[Hepatobiliary scintigraphy: a functional test]. / Scintigraphie hépatobiliare: test fonctionnel.

99mTc-diethyl-HIDA selective captation by hepatocytes and rapid excretion into bile provides a scintigraphic imaging of liver, biliary system and gall bladder. Substance blood clearance and liver half-life measurements add quantitative information on liver function. Normal, cirrhotic and jaundiced patients with extrahepatic obstruction were studied and each group showed significant characteristics. Through non-invasive biliary system visualization and liver function evaluation, hepatobiliary scintigraphy has its place as a complementary investigation in hepatology.

Differential diagnosis of xerostomia by quantitative salivary gland scintigraphy.

A new and rapid method of quantitative salivary gland scintigraphy has been developed. The uptake of pertechnetate in the glandular tissue and in a reference area in the neck are measured. The ratio between these measurements gives an index of salivary gland activity. By using this activity index, quantitative information on the functional state of the parotid and submandibular glands can be obtained. In cases of xerostomia such measurements may be particularly helpful in differentiating Sjögren's syndrome and sialosis and hence in the choice of appropriate treatment.