Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Patent
1993-05-12
1995-06-20
Geist, Gary
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
534 10, 534 14, A61K 5104, C07F 1300
Patent
active
054259355
DESCRIPTION:
BRIEF SUMMARY
This invention relates to imaging and is particularly concerned with diagnostic imaging of infections with metallic radionuclides.
BACKGROUND OF THE INVENTION
The detection and identification of sites of bacterial infection, for example in a post-operative patient, has long been problematic. Thus the methods currently available for such diagnosis, such as scintigraphic scanning using radionuclides (e.g. Tc-99m and Ga-67) and radiolabelled Antibodies, are not specific in that they do not provide a means of distinguishing between infection foci and centres of inflammation. A specific method is available involving the In-111 oxime labelling of removed and purified white blood cells which are then reintroduced to the patient. Such a method is time-consuming and requires skilled manipulation in order to obtain a satisfactory result. It is important to differentiate between the two conditions, because there is bacterial involvement in infection, whereas inflammation, while sometimes following on from infection, is often attributable to mechanical damage. Thus the follow-up treatment differs for infection and inflammation and may be critical.
DESCRIPTION OF THE INVENTION
The present invention provides an entirely new solution to this problem in that it makes use of radionuclide-labelled antibiotics to specifically target sites of bacterial infection as opposed to inflammation and thus give a means of early identification of infection. Antibiotics are by no means the obvious candidate for use in radionuclide imaging. They are usually semi-synthetic in structure (for example, the penicillins) and do not lend themselves to complex formation with metals. They can cause the build up of resistance and sensitisation in the body. Furthermore, they are designed with a view to attaining therapeutic concentrations in most tissues of the body, rather than with a view to giving uptake purely at the sites of infection. It is not necessarily apparent that they are capable of giving a good target to background ratio.
According to the present invention, there is provided, for use in gamma ray scintigraphy diagnostic Imaging of a patient with a metallic radionuclide, a 4-quinolone antibiotic compound or a pharmacologically acceptable salt thereof.
The 4-quinolone antibiotics are a known class of antibacterial agents and those antibiotics-of this type which have already been recognised are reviewed by Chu et al., Antimicrobial Agents and Chemotherapy, 33, No. 2, 1989, 131-135. Thus the term "4-quinolone antibiotic" is intended to include structures containing the quinolone, naphthyridine and benzoxazine ring systems. Preferred quinolones are those bearing a 3-carboxy substituent, and preferably also a halogen substitutent at the 6-position, especially fluorine.
A preferred subgroup of 4-quinolone antibiotics are those having formula I: ##STR1## in which R.sup.1 is a cyclic or acylic hydrocarbyl group which may be substituted, R.sup.2 is hydrogen or an alkyl group, X represents a halogen atom, and Y is a nitrogen atom or a group .dbd.CR.sup.3 where R.sup.3 is hydrogen or an alkyl group, or R.sup.1 and R.sup.3, together with the ring carbon and nitrogen atoms to which they are attached, form a carbocyclic or heterocyclic ring, which may be substituted, or an optically active isomer of such a compound or a pharmaceutically acceptable salt of such a compound.
The halogen atom is preferably-fluorine.
One preferred example of a suitable antibiotic of formula I is that known as ciprofloxacin, which is a compound of formula I in which R.sup.1 is cyclopropyl, Y is .dbd.CH.sub.2, X is fluorine and R.sup.2 is hydrogen. Further preferred examples are the compound of formula I in which Y is CR.sup.3 and R.sup.1 and R.sup.3 together with the C and N atoms to which they are attached form a 2-methyl morpholino ring, X is fluorine and R.sup.2 is methyl (known as ofloxacin) or the compound of formula I in which R.sup.1 is ethyl, X is fluorine, Y is .dbd.CH.sub.2 and R.sup.2 is hydrogen (known as norfloxacin).
These quinolone antibiotics are pu
REFERENCES:
patent: Re31463 (1983-12-01), Loberg et al.
patent: 5093105 (1992-03-01), Flanagan et al.
patent: 5153203 (1992-10-01), Yatsunami et al.
patent: 5233091 (1993-08-01), McGuirk
patent: 5245026 (1993-09-01), Johnson et al.
patent: 5245037 (1993-09-01), Kuramoto et al.
patent: 5262417 (1993-11-01), Gammill et al.
patent: 5300644 (1994-04-01), Hermecz et al.
Solomons, Organic Chemistry (4th Ed.), 1988, pp. 689-690.
H. M. Siefert et al "Pharmacokinetics of ciprofloxacin . . . " Abstract #12256h, Chemical Abstracts, vol. 106 No. 3, 13 Jan. 1987 (Columbus, Ohio, USA) p. 12.
T. Fujii et al "Distribution of (14C)AT-2266 . . . " #103538q, Chemical Abstracts, vol. 101 No. 13, 24 Sep. 1984 (Columbus, Ohio, USA), p. 13.
D. T. W. Chu et al "Structure-activity relationships . . . " Anticmicrobial Agents & Chemotherapy, vol. 33 No. 2, Feb. 1989 (Washington, D.C., USA) pp. 131-135.
G. Hoffken et al "Reduced enteral absorption . . . " European Jour. of Clin. Microbiology, vol. 4 No. 3, Jun. 1985 (Wiesbaden, DE), p. 345.
British Technology Group Limited
Chapman Lara E.
Geist Gary
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