FDA approves isotope fo heart diagnosis Thallium-201, a radioactive isotope that is useful in diagnosing heart disease, has received Food & Drug Administration approval for routine clinical use. New England Nuclear Corp., the Boston-based manufac turer of the isotope, says that it has proved safe and effective in clinical testing over the past five years. Thallium-201 is seen as an adjunct to angiography, a technique requiring hospitalization and which involves following blood flow to the heart muscle with x-rays and a radioactively opaque dye. Unlike angiogra phy, which requires insertion of catheters into a patient's blood ves sels, thallium-201 is given by simple injection. Shortly thereafter, three photo images of the patient are taken to reveal how the isotope makes its way into the heart muscle. The technique works so simply, according to New England Nuclear, because the isotope mimics potassium ion. The ions are taken up normally from the blood stream into cells of the heart. Abnormalities such as dam aged heart-muscle cells or malfunc tioning blood vessels are revealed when the isotope fails to chart its way into or through them.
The isotope is particularly useful for determining the occurrence or extent of a heart attack, providing information that electrocardiograms cannot give. Thus, for example, sec tions of the heart muscle that might be damaged by a mild attack won't take up the isotope because cells there are dead, New England Nuclear ex plains. That can pinpoint the severity of the attack quickly and without stressing the patient. Clinical testing with the thallium isotope is cheaper than is angiogra phy. It also involves lower exposure to radiation for the patient. Thallium201 has a 73-hour half-life and thus effectively disappears quickly from the body. Use of thallium-201 is not expected to replace angiography, however. Angiography is still superior for lo cating sites of blockage in blood ves sels supplying the heart. Moreover, angiography is done dynamically, showing blood flow. Thallium-201 images are static, though several can be taken in sequence. According to New England Nuclear, the new pro cedure "provides information com plementary to that obtained by an giography." D
Industry group offers car inogens policy The American Industrial Health Council (AIHC), an industry group representing more than 70 chemical makers and users, has offered alter natives to the Occupational Safety & Health Administration's proposals for regulating potential carcinogens in the workplace. Although AIHC doesn't maintain that no problems exist, spokesmen for the group stress that a zero risk con cept, which is perceived by industry as implicit in many of the govern ment's proposed regulations, is "un realistic." In line with this thinking, the council submitted a number of its proposals to OSHA earlier this month, even though the agency plans to hold hearings on its carcinogens policy no sooner than April. Among AIHC's suggestions: • Develop dose-response data to establish a no-effect level of exposure to carcinogens. Current thinking in the government is that there is no no-effect level for a carcinogen. • Carcinogens vary in potency, therefore they should be regulated according to relative hazard. Federal agencies generally don't accept this concept. • Animal toxicology data are valuable, but epidemiological data 6
C&EN Jan. 23, 1978
concerning a potential carcinogen are often more valuable in determining a cancer hazard to workers. Many fed eral regulatory decisions, however, are based largely on animal studies. • Short-term in vitro tests, such as the Ames test, for potential carcino gens are useful as screening tools, but should not be the sole basis for regu latory decisions. There is some rec ognition of this caveat by federal agencies. • The use of personal protective equipment by workers in many cases may be more efficient than imposing rigid engineering controls to protect workers from exposure to carcino gens. Previous actions by the gov ernment—for example, the strict limits on vinyl chloride emissions— don't augur well for adoption of such a policy. Thus, although AIHC proposals appear to be an industrial wish list, the council concedes that "identifying and regulating carcinogens in the workplace is a formidable but most necessary task, one that requires the best thinking of the most informed representatives of science, govern ment, labor, business, and public in terest groups." It's important, too, according to Dow Chemical U.S.A.
president Paul F. Oreffice, a member of the council's steering committee, because "in effect, OSHA is writing a national standard for carcinogens." Oreffice believes that other agencies will pattern their regulations after the OSHA proposals. Π
Abbott gets approval to market urokinase The Food & Drug Administration has approved Abbott Laboratories' new drug application for urokinase, a blood clot-dissolving agent (C&EN, March 1, 1971, page 18). The North Chicago, 111., pharmaceutical firm will market the drug under the brand name Abbokinase. The company notes that the drug has been approved only for treatment of massive pulmonary embolism. That disease, which occurs when a blood clot blocks a pulmonary artery or one of its branches, causes fluid to accumulate in the lungs and prevents proper oxygenation of the blood. Ac cording to various estimates, pulmo nary embolism causes 150,000 to 200,000 deaths in the U.S. each year. Urokinase works by activating the body's system for breaking up fibrin, the protein that is the essential part of a blood clot, Abbott explains. Ad ministered intravenously, the drug converts plasminogen, an inactive substance in the blood, into plasmin, a proteolytic enzyme with high spec ificity for fibrin. The enzyme, in turn, converts fibrin into soluble products that are carried away in the blood. Abbott points out that the action of urokinase is different from that of anticoagulants, such as heparin. The latter can help prevent formation of clots, but can't dissolve clots that al ready have formed. Urokinase is itself an enzyme, produced by the kidneys and nor mally found in minute quantities in urine. The drug can be—and is— obtained by extraction from urine. Urine-derived urokinase has been marketed in Japan and Europe for several years. Another U.S. drug firm, Sterling Winthrop, has filed a new drug application for urine-derived urokinase. However, Abbott produces the drug from human kidney cells grown in tissue culture. That process is more efficient, the company says. FDA's approval of urokinase cul minates more than a decade of re search and development, including clinical trials that began in 1968, Abbott says. The company will con tinue clinical studies to determine the effectiveness of the drug in treating other thrombotic disorders. D
