Introduction

In 1977, the “Father” of PE diagnosis in Nuclear Medicine, George V. Taplin, used a new PET tracer ¹⁵O labelled CO₂ and a Pertechnetate aerosol to examine experimental PE in dogs . The proof of concept was validated for the ¹⁵O in humans three years later from HW (Bill) Strauss’ Department in Boston . The hope was that this clear demonstration of an inhalation only test for PE would lead to a much more convenient and less fallible diagnosis than the then current attempts at V/Q with a plethora of ventilation agents.
Any test using ¹⁵O was not going to come into general clinical practice because of the radionuclide’s 2.1min half life. But the concept of an inhalation only test for PE was validated. Taplin’s paper reported a successful use of pertechnetate aerosol (TcO-4) in his experimental dog emboli, but unlike the C¹⁵O₂ the test did not transfer to clinical studies. The reasons for this failure were almost certainly due to the limitations of the technology, essentially the inability to get a high enough specific activity into the lung in a single breath, and not the fundamental physiology of a PE. But it will be important to consider delay after the onset of a PE as a factor mitigating against the concept since the collateral bronchial circulation can begin to take over the pulmonary function after a few hours.
This proposal revisits the exciting prospect of a new imaging test for PE, requiring a single breath inhalation only, taking account of developments in high specific activity diffusible tracers and imaging technology, both in terms of hardware and software. If adopted, it will lead to a simple procedure creating a “hot spot” image, pathognomonic of Pulmonary Embolism. Hot Spot imaging is the ultimate aim of all Radiopharmaceutical tracer development, and to achieve this simply in PE diagnosis would be a major breakthrough.

The Proposal

• There are two options available to pursue the goal of a “single breath inhalation only” imaging procedure for diagnosing PE. The first is to use an existing technology, Pertechnegas, and the second is to create a new microaerosol de novo. Pertechnegas, on inhalation, is a highly diffusible, soluble microaerosol Oxide of Technetium which forms TcO4- on contact with water vapour and the alveolar mucous surface in the lung. It diffuses rapidly and mono-exponentially into the pulmonary circulation with a half-time clearance of 10 minutes in normal perfused lung . It has been used clinically for many years to diagnose alveolar-capillary membrane permeability changes in diseases like fibrosing alveolitis as in those conditions it exhibits a much faster clearance rate, and a few centres have used it as a ventilation agent in conjunction with labeled MAA perfusion in the standard V/Q imaging procedure. But the imaging time constraints made it much less attractive in a routine clinical setting than Technegas, produced in the same machine, so it did not become widely used.
  • It is a trivial process to create a single breath concentration of Pertechnegas in a standard Technegas generator
  • Multihead SPECT cameras are now widespread and their associated computing power will enable real time wash-out correction on a pixel by pixel basis to create a “hot spot” PE image directly.
  A clinical trial to establish the validity of this proposal could be run very quickly and cheaply. Two sets of images, taken 10 minutes apart, and superimposed, would reveal those regions of delayed wash-out, indicating a static blood pool. “Hot-spots” caused by COPD would be readily differentiated by their position and activity invariance. Indeed it may well be that the test is so sensitive, SPECT is an unnecessary sophistication, since we are only looking for the presence of one or more “hot-spots”.
  
• Taplin GV, Chopra SK, Elam D. “Imaging experimental pulmonary ischemic lesions after inhalation of a diffusible Radioaerosol: concise communication” J Nucl Med 18: 250-254, 1977.
  
• Nichols AB, Bellar GA et al. “Detection of Pulmonary Emboli by Positron Imaging of inhaled 15O-labelled Carbon Dioxide”. Sem Nucl Med 10: 252-258, 1980.
  
• Kotzerke J, Van Der Hoff J, Burchett W, et al. A compartmental model for alveolar clearance of Pertechnegas. J. Nucl Med 37:(12) 2066 - 2071, 1996.