Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Attached to cyclopentano-hydrophenanthrene ; derivative thereof
Patent
1991-02-05
1994-07-05
Stoll, Robert L.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Attached to cyclopentano-hydrophenanthrene ; derivative thereof
424 169, A61K 4902
Patent
active
053265513
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Specific secretory granules of mammalian atrial cardiocytes contain peptides which possess natriuretic and diuretic activities in mammals, including man. One or more peptides have been called atrial natriuretic factor (ANF) or, interchangeably, atrial natriuretic peptide (ANP). In all mammals which have been studied ANF has a similar amino acid sequence but may differ in the amino acid composition at several positions. ANF has been identified as possessing several useful anti-angiotensinogenic properties. It is an effective vasodilator, natriuretic and diuretic agent as well as having other potential activities (as further discussed below).
Atrial natriuretic factor has been isolated from both human and animal sources, and its vasodilating, natriuretic and diuretic utility has been well documented. It has also been discovered that hypertensive humans and animals respond to injection of ANF to a much greater extent than do normotensive subjects. ANF has accordingly been considered potentially useful in treating hypertension and other diseases relating to a salt-water imbalance in the body. (These properties are summarized in review articles of two of the inventors herein, Dr. Johanne Tremblay and Dr. Pavel Hamet, published in "Medicographia" (1986) 8(3) and in "Nephrologie" (1987) 8:7-12).
ANF can be radioiodinated on tyrosine residues. U.S. Pat. No. 4,609,725 (Inventors: Brady, S. F. et al) which issued on Sep, 2, 1986, relates to atrial natriuretic factor and fragments thereof. Mono-iodinated-tyrosine derivatives of these peptides and fragments are described in this patent as being useful in the study of the metabolic half-life of ANF in clinical and in vitro studies.
It is known that ANF binding or uptake is tissue specific in the body. In particular, the renal glomeruli and the distal tubule of the nephron have specific binding sites (receptor sites) for ANF. Other organs which also selectively bind ANF include blood vessels, the lungs, the brain, the heart, the outer cortex and medulla of the adrenal gland, the liver and the gonads (see J. Genest and M. Cantin: The Artial Natriuretic Factor; its Physiology and Biochemistry, in Review of Physiology, Biochemistry and Pharmacology (Genest J., Cantin M. Eds), Springer-Verlag Heidelberg, Berlin, 1988). These target organs possess more ANF receptors or binding sites than other organs.
This selective binding of ANF to target organs in humans and other mammals could be useful in the identification and diagnosis of certain conditions and pathologies, and in identifying and diagnosing anomalies of target organs. It is known that ANF receptors are abnormal in the kidney during hypertension and diabetes (see, for example, Swithers, Stewart and McCarty, Life Sci. 40, 1673 (1987)) .
OBJECTS OF THE INVENTION
This invention seeks to provide a method of diagnosing or monitoring diseases in which there is a change in ANF receptor activity in a target organ by administering radio-labelled ANF (or an active fragment or analog thereof) and measuring the kinetics of binding of the radio-label in the target organ.
This invention also seeks to provide a method of diagnosing or monitoring diseases in which there is a change in ANF receptor activity in a target organ by administering radio-labelled and/or non-radio-labelled ANF (or an active fragment or analog thereof) and measuring the displacement of radio-labelled by non-radio-labelled ANF (or fragment or analog thereof).
This invention further seeks to provide compositions and kits comprising radio-labelled ANF (or an active fragment or analog thereof) which may be used in diagnosing or monitoring diseases, especially diseases of the kidneys and lungs.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a nuclear imaging method for quantifying uptake, binding, displacement or wash out of atrial natriuretic factor in target organs of mammals. In a first step, there is administered a diagnostically effective amount of radio-labelled atrial natriuretic factor or active fragme
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Hamet Pavel
Lamberet Raymond
Leveille Jean
Tremblay Johanne
Cooper Iver P.
Covert John M.
L'Hotel-Dieu de Montreal
L'Istitut de Recherches Cliniques de Montreal
Stoll Robert L.
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