NZ228059A

NZ228059A - Inhalable radiolabelled antibodies for locating lung tumours

Info

Publication number: NZ228059A
Application number: NZ22805983A
Authority: NZ
Inventors: Mark Philip Best
Original assignee: Mark Philip Best
Priority date: 1983-04-20
Filing date: 1983-04-20
Publication date: 1990-11-27

Description

New Zealand Paient Spedficaiion for Paient Number £28059 22 8 0 5 9 Under the provisions of Regulation 23 (1) ths Specification has been ante-dated to jS...Ap.d 19 M. h^ls Patents Form No. 5 PATENTS ACT 1953 COMPLETE SPECIFICATION No.: r Date: 20/4/83" ...

DIVISIONAL OUT OF'NEW ZEALAND PATENT APPLICATION 203949 LUNG IMAGING WITH RADIO LAB EL LED AGENTS I, MARK PHILIP BEST, of 146 Caversham Valley Road, Dunedin, New Zealand, a New Zealand citizen, hereby declare the invention, for which I pray that a Patent may be .granted to me and "the method by which it is to be performed, to.be particularly . described in and by the following statement: 22 8 0 59 This invention relates to a method of diagnosing lung disorders, and more particularly, to a method for diagnosing lung tumors.

It is to be understood that the term "lung" includes all of the respiratory air passages.

It is an object of this invention to provide a means for diagnosing lung disorder, particularly tumors.

According to this invention, there is provided a method of diagnosing an abnormality in a patient's lung comprising subjecting a patient to a radiolabelled agent by .ventilation the radiolabelled agent being retained at the locality of the abnormality, but being otherwise removed by body function, the patient then being subjected to a detection means adapted to record the presence of the retained agent and which thereby provides diagnostic information.

Other objects of this invention which should be considered in all of its novel aspects will become apparent from the description which is given by way of example of one embodiment of the invention.

Modifications and developments are envisaged and may be incorporated without departing from the scope or spirit of the invention for example methods to enhance sedimentation or impaction of the deposited radiopharmaceutical can be incorporated into the inhalation method, eg slowing inhalation velocity and minimising depth of breath. This can enhance 228059 deposition on the mucociliary clearance mechanism and reduce alveolar deposition where clearance is found to be slow. The presently preferred embodiment relates to the use of radio-labelled antibodies which have been selected so as to be lung tumor specific. It is known that small cell tumors of the lung produce bioactive substances. It has long been the goal of workers to use radiolabelled antibodies to such substances to permit detection of tumors. It is known also that one such substance produced by lung tumors is the hormone calcitonin.

According to the invention there is additionally provided a radiolabelled antibody in a form suitable for inhalation.

According to the preferred embodiment an aerosol comprising calcitonin-specific antibodies which have been radiolabelled by technetium 99 is prepared.

Figure one is a diagrammatic representation of the prepared method of preparation of the radiolabelled antibodies. The following is a non-limiting example of preparations of the composition of this invention and of the use thereof. Goat antisera against synthetic human calcitonin (Ciba-Geigy) was affinity purified using calcitonin covalently linked to cyanogen bromide activated sepharose. Labelled antibodies were recovered using 6M Guanidine in phosphate buffered saline and dialysed. Labelling with technetium 99m was by stannous reduction and immunoreactivity confirmed by radioimmunossay and immunodiffusion- 150 MBq of Tc99m 22 8 0 5 9 labelled antibody was delivered to the lungs in an aerosol generated by a compressed air nebuliser and passed through drying and sedimentation chambers.

The patient is caused to inhale this aerosol by means of ventilation apparatus. Deposition of the aerosol on the lung surfaces occurs, with normal mucociliary clearance acting to remove the aerosol. Where tumors exist in the lung, the radiolabelled antibody is localised with immunoreactivity by the tumor (the focus of antigen concentration eg calcitonin) thereby becoming targeted and fixed in proximity to the tumor site. Imaging with, a gamma radiation detecting camera then shows the higher concentration of the antibody at the tumor site.

It is desirable to allow a period of time to elapse to allow normal mucociliary clearance to remove at least a significant amount of the unlocalised radiolabelled antibody and hence increase the contrast between the localised antibody and background. It has been observed that the rate of clearance of unbound antibody is dependant on the particle size. Below an optimum particle size such clearance takes a long time to occur.

It has been found that the optimum particle size range for inhalation is 0.2 microns to 1.4 microns. It is observed that particles of diameter greater than 2.0 microns lend to impact in the upper airways and throat of the subject. Particles of diameter less than 0.2 microns tend to deposit

Claims

22 8 on the alveolar surfaces which manifest slow clearance. Desirably the clearance period is as short as possible >such as 18 to 24 hours. As an alternative to an aerosol, a fine powder able to be inhaled containing the radiolabelled antibody may usefully be employed; the fine powder . being in a form suitable for inhalation through an inhalation device such as a rotary inhalation device. The basic principle of the invention is as set forth in the attached claims and the manifestation of the invention as described is intended to be by way of example only. 228059 - 6 - WHAT I CLAIM ISt

1. A radiolabelled agent for use in the diagnosis of lung disorders which comprises radiolabelled antibodies in a form suitable for inhalation.

2. A method for the preparation of a diagnostic inhalation agent as claimed in claim 1 comprising: (a) Raising antibodies to a hormone produced by a tumour of human lung cells; (b) Radiolabelling said antibodies; and (c) Passing a solution containing said radiolabelled antibodies through a compressed air nebuliser, and forming an aerosol thereby.

3. A method as claimed in claim 2 in which the lung tumour hormone is calcitonin, the radiolabelling is with technetium 99m and the aerosol particle size range is 0.2 microns to 1.4 microns.

4. A diagnostic aerosol prepared according to either claim 2 or claim 3.

5. A method for the preparation of a diagnostic inhalation agent as claimed in claim 1 comprising: (a) Raising antibodies to a hormone produced by a tumour of human lung cells; (b) Radiolabelling said antibodies; and (c) Passing a powder containing said radiolabelled antibodies through an inhalation device, to form an inhalation composition of airborne particles.

6. A method as claimed in claim 5 in which the lung tumour hormone is calcitonin, the radiolabelling is with technetium 99m and the airborne particle size range-is 0.2 microns to 1.4 microns. -V. • 228059 - 7 -

7. A radiolabelled agent as claimed in claim 1 in which the radio label is technetium 99m and the antibodies are' calcitonin specific.

8. A radiolabelled agent as claimed in claims 1 or 7 in which said form is an aerosol.

9. A radiolabelled agent as claimed in claims 1 or 7 in which said form is a powder.

10. A diagnostic system for detecting the presence of a lung tumour hormone comprising: (a) A radiolabelled agent as claimed in claim 1; (b) Detection means for detecting said radiolabelled antibodies; (c) Recording means which record the locations of such detected radiolabelled antibodies.

11. A diagnostic system as claimed in claim 10 in which the recording means is a gamma radiation detecting camera.

12.' The records produced by the diagnostic . system as claimed in claim 10 or claim 11. MARK PHILIP BEST By his attorneys BALDWIN, SON & CAREY 228059 AFRNUY LABELLING OF Tc 99m-ANTlCAL£ITONIN Calcitonin Antiserum ^ - isolation of + S§ CT OO Troom Tc99m Tc99m$ SSL $ Tc99m Tc99m SnCl2/Tc99m labelling Tc99m LABELLING O BEAD=Anti CT-Glass Wool - 8 WASH ! \ SnCLi 2 f Tco^ 3 If PBS 4.116M GUANONE (GuHCO RENATURATION c „ „ Tc99m Tc 99m " 3uKI ^fc99m DRY 'Sephadex'— BEADS at* regain volume Tc99mO tPBS £>Tc99m £>Tc99m Otc 99m MARK PHILIP BEST by his attorneys., Baldwin, Son & Ca'rey (5bu7}^S&^