REVIEW OF THE CURRENT PRACTICE OF THE INHALATIONAL USE OF POSITRON EMITTERS

Abstract

Purpose: In this paper, I am reviewing the current state of art of use of PET imaging in inhalational studies, exploring the potential for this imaging modality in the respiratory field.

Inhalational delivery is a commonly used method of drug administration, especially for conditions that affect the lung where optimal lung drug exposure is desired, for example steroids in chronic obstructive pulmonary disease or bronchial asthma ⁽²⁾ or for conditions where the kinetics of systemic therapy has limited access to lungs in conditions such as idiopathic pulmonary fibrosis ⁽³⁾. 

Approach: I searched the literature, using PubMed and MEDLINE databases, for papers and publications looking into the inhalational use of positron emitters over the last two decades.

Results: There has been a quest recently to administer drugs through inhalational methods as an alternative to systemic administration allowing more effective dosing levels with reduced systemic toxicity ⁽⁴⁾. Nuclear imaging methods such as Single Photon Emission computed tomography (SPECT) and PET, have been used to assess aerosol delivery to the lung. Higher sensitivity, the ability for dynamic acquisition and physiological respiratory gating confers an advantage to PET ⁽⁷⁾. 

The biodistribution in the lungs of a number of radiolabeled agents administered via inhalation such as [11C] triamcinolone, [18F] fluticasone, [11C] zanamivir has been evaluated using PET ^(8-11).  Inhalational biodistribution of FDG has also been investigated in conditions such as cystic fibrosis and lung inflammation ⁽¹¹⁾. 

Conclusions: There are currently continuing advancements in radiotracer development and imaging technologies which offer promising avenues for enhancing drug delivery via inhalation.

Keywords:

Positron Emission Tomography, Inhalational

References

Lee-Wong M, Dayrit FM, Kohli AR, Acquah S, Mayo PH. Comparison of high-dose inhaled flunisolide to systemic corticosteroids in severe adult asthma. Chest. 2002;122(4):1208-13.

Brun EHC, Hong ZY, Hsu YM, Wang CT, Chung DJ, Ng SK, et al. Stability and Activity of Interferon Beta to Treat Idiopathic Pulmonary Fibrosis with Different Nebulizer Technologies. J Aerosol Med Pulm Drug Deliv. 2023.

Qin L, Cui Z, Wu Y, Wang H, Zhang X, Guan J, et al. Challenges and Strategies to Enhance the Systemic Absorption of Inhaled Peptides and Proteins. Pharm Res. 2022:1-19.

Nelson HS. Inhalation devices, delivery systems, and patient technique. Ann Allergy Asthma Immunol. 2016;117(6):606-12.

Costa A, Pinheiro M, Magalhaes J, Ribeiro R, Seabra V, Reis S, et al. The formulation of nanomedicines for treating tuberculosis. Adv Drug Deliv Rev. 2016; 102:102-15.

Dolovich MB, Bailey DL. Positron emission tomography (PET) for assessing aerosol deposition of orally inhaled drug products. J Aerosol Med Pulm Drug Deliv. 2012;25 Suppl 1: S52-71.

Berridge MS, Lee Z, Heald DL. Pulmonary distribution and kinetics of inhaled [11C] triamcinolone acetonide. J Nucl Med. 2000;41(10):1603-11.

Berridge MS, Lee Z, Heald DL. Regional distribution and kinetics of inhaled pharmaceuticals. Curr Pharm Des. 2000;6(16):1631-51.

Bergstrom M, Cass LM, Valind S, Westerberg G, Lundberg EL, Gray S, et al. Deposition and disposition of [11C] zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography. Clin Pharmacokinet. 1999;36 Suppl 1:33-9.

Dolovich MB. 18F-fluorodeoxyglucose positron emission tomographic imaging of pulmonary functions, pathology, and drug delivery. Proc Am Thorac Soc. 2009;6(5):477-85.

Woolley GE, C. Brown, N. France, L. Wright, G. Archibald, S. Development of a dynamic lung phantom for use in lung ventilation studies. Soceity of Nuclear Medicine and Molecular Imaging Vancouver: Journal of Nuclear Medicine; 2022.

Woolley GH, G. Roberts, D. Domarkas, J. Wright G, Archibald, S., editor. British Nuclear Medicine Society Spring Meeting 2022; May 2022: Nuclear Medicine Communications.

Rahmim A ZH. PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun. 2008;29(3):193-207.

Bailey DL, Eslick EM, Schembri GP, Roach PJ. (68) Ga PET Ventilation and Perfusion Lung Imaging-Current Status and Future Challenges. Semin Nucl Med. 2016;46(5):428-35.

Ebner L, Kammerman J, Driehuys B, Schiebler ML, Cadman RV, Fain SB. The role of hyperpolarized (129) xenon in MR imaging of pulmonary function. Eur J Radiol. 2017; 86:343-52.

Aliyu SA. Positron Emission Tomography (PET) in Non-malignant Chest Diseases: University of Hull and University of York; 2019.

Capitanio S, Nordin AJ, Noraini AR, Rossetti C. PET/CT in nononcological lung diseases: current applications and future perspectives. European Respiratory Review. 2016;25(141):247-58.

Scheuch G, Bennett W, Borgström L, Clark A, Dalby R, Dolovich M, et al. Deposition, imaging, and clearance: what remains to be done? J Aerosol Med Pulm Drug Deliv. 2010;23 Suppl 2: S39-57.

Lee Z, Berridge MS, Finlay WH, Heald DL. Mapping PET-measured triamcinolone acetonide (TAA) aerosol distribution into deposition by airway generation. Int J Pharm. 2000;199(1):7-16.

Irene Hernández-Lozano SM, Thomas Filip, Michael Sauberer, Thomas Wanek, Johann Stanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer. PET imaging to assess the impact of P-glycoprotein on pulmonary drug delivery in rats. Journal of Controlled Release. 2022; 342:44-52.

Le Roux PY, Hicks RJ, Siva S, Hofman MS. PET/CT Lung Ventilation and Perfusion Scanning using Galligas and Gallium-68-MAA. Semin Nucl Med. 2019 Jan;49(1):71-81. doi: 10.1053/j.semnuclmed.2018.10.013. Epub 2018 Nov 17. PMID: 30545520.

Blanc-Béguin F, Damien P, Floch R, Kerleguer K, Hennebicq S, Robin P, Salaün PY, Le Roux PY. Radiation exposure to nuclear medicine technologists performing a V/Q PET: Comparison with conventional V/Q scintigraphy, [18F] FDG PET and [68Ga]Ga DOTATOC PET procedures. Front Med (Lausanne). 2022 Nov 30; 9:1051249. doi: 10.3389/fmed.2022.1051249. PMID: 36530884; PMCID: PMC9747754.

Mintun MA, Raichle ME, Martin WR, Herscovitch P. Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med. 1984;25(2):177-87.

Agostini D, Iida H, Takahashi A, Tamura Y, Henry Amar M, Ono Y. Regional myocardial metabolic rate of oxygen measured by O2-15 inhalation and positron emission tomography in patients with cardiomyopathy. Clin Nucl Med. 2001;26(1):41-9.

Hofman MS, Beauregard J-M, Barber TW, Neels OC, Eu P, Hicks RJ. ⁶⁸Ga PET/CT Ventilation–Perfusion Imaging for Pulmonary Embolism: A Pilot Study with Comparison to Conventional Scintigraphy. Journal of Nuclear Medicine. 2011;52(10):1513-9