A generator for the production of radiolabelled ultrafine carbonaceous particles for deposition and clearance studies in the respiratory tract

Abstract A generator for the production of radiolabelled ultrafine carbonaceous particles for inhalation and clearance studies is described. A Technegas generator in combination with 99 m Tc labelling is a device used in clinical routine to investigate the ventilation of the human lung. However, under standard operating conditions the Technegas generator does not provide ultrafine particles with a stable radiolabel. The removal of saline from the Tc-eluate by an ion exchange column yielded low leaching rates of the radiolabel from the particles of below 4% within 24 h (12% under standard conditions) and guaranteed non-hygroscopic aerosol properties. Short burning times (2 s; standard 15 s) and immediate dilution of the generated aerosol into a conductive bag yielded stable ultrafine particles in the size range between 40 and 100 nm count median diameter (standard 200 nm), with a geometric standard deviation of 1.6. We adapted the generator to a bolus inhalation system, allowing regional aerosol deposition into different lung regions and appropriate clearance studies. In addition the particles can be labelled by 111 In instead of 99 m Tc, extending the investigation time of clearance studies from 1 day to some weeks.

[1]  Kazuyoshi Suga,et al.  Technical and analytical advances in pulmonary ventilation SPECT with xenon-133 gas and Tc-99m-Technegas , 2002, Annals of nuclear medicine.

[2]  W. Kreyling,et al.  Inhalation of salt aerosol particles—II. growth and deposition in the human respiratory tract☆ , 1988 .

[3]  H. E. Palmer,et al.  Distribution and excretion of technetium in humans. , 1966, Health physics.

[4]  D. Dockery,et al.  An association between air pollution and mortality in six U.S. cities. , 1993, The New England journal of medicine.

[5]  R. Harrison,et al.  The generation and characterisation of elemental carbon aerosols for human challenge studies , 2003 .

[6]  W. Kreyling,et al.  TRANSLOCATION OF ULTRAFINE INSOLUBLE IRIDIUM PARTICLES FROM LUNG EPITHELIUM TO EXTRAPULMONARY ORGANS IS SIZE DEPENDENT BUT VERY LOW , 2002, Journal of toxicology and environmental health. Part A.

[7]  W M Burch,et al.  Technegas - a new ventilation agent for lung scanning , 1986, Nuclear medicine communications.

[8]  Klaus Willeke,et al.  Aerosol Measurement: Principles, Techniques, and Applications , 2001 .

[9]  F. Löffler,et al.  Investigations of a new aerosol generator for the production of carbon aggregate particles , 1993 .

[10]  G. Willett,et al.  Physical properties and use of pertechnegas as a ventilation agent. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  T. Isawa,et al.  Technegas Versus Krypton‐81m Gas as an Inhalation Agent: Comparison of Pulmonary Distribution at Total Lung Capacity , 1994, Clinical nuclear medicine.

[12]  C. Roth Generation of ultrafine gold aerosols , 1986 .

[13]  Annette Peters,et al.  Epidemiological evidence of the effects of ultrafine particle exposure , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[14]  W. Kreyling,et al.  Translocation of Inhaled Ultrafine Particles to the Brain , 2004, Inhalation toxicology.

[15]  Shinji Takenaka,et al.  Generation of Ultrafine Particles by Spark Discharging , 2004 .

[16]  C. Roth,et al.  Radioactively labelled ultrafine particles for clearance measurements , 1990 .

[17]  K. Hiraga,et al.  High‐resolution electron microscopy of technegas and pertechnegas , 1996, Nuclear medicine communications.

[18]  M. Ohkawa,et al.  Tc-99m Technegas scintigraphy to evaluate the lung ventilation in patients with oral corticosteroid-dependent bronchial asthma , 1999, Annals of nuclear medicine.

[19]  Wolfgang G Kreyling,et al.  Dosimetry and toxicology of ultrafine particles. , 2004, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[20]  W. Kreyling,et al.  Deposition and clearance of fine particles in the human respiratory tract , 1997 .

[21]  T. Isawa,et al.  Inhalation of pertechnegas: Similar clearance from the lungs to that of inhaled pertechnetate aerosol , 1995, Nuclear medicine communications.

[22]  M. Lemb,et al.  Technegas: a study of particle structure, size and distribution , 1993, European Journal of Nuclear Medicine.

[23]  J. Heyder,et al.  Aerosol derived airway morphometry in healthy subjects. , 1995, The European respiratory journal.

[24]  W. Burch Evidence for the long-term biological distribution of Technegas particles. , 1993, Nuclear medicine communications.

[25]  W. Bennett,et al.  Generation of Radiolabeled "Soot-Like" Ultrafine Aerosols Suitable for Use in Human Inhalation Studies , 2000 .

[26]  James S. Brown,et al.  Ultrafine particle deposition and clearance in the healthy and obstructed lung. , 2002, American journal of respiratory and critical care medicine.

[27]  Robert Gelein,et al.  EXTRAPULMONARY TRANSLOCATION OF ULTRAFINE CARBON PARTICLES FOLLOWING WHOLE-BODY INHALATION EXPOSURE OF RATS , 2002, Journal of toxicology and environmental health. Part A.