Galligas and Hot Spot imaging for PE

The first clinical report using the positron emitter 68Ga within a Technegas generator was published as a letter (PET aerosol lung scintigraphy using Galligas. J. Kotzerke, M. Andreeff, G. Wunderlich., 2010, Eur J Nucl Med Mol Imaging  37: 175-177) and demonstrates very clearly the concept of encapsulating a range of radionuclides within the graphitic cocoon.

A Gallium-68 generator is a device used to extract the positron-emitting isotope 68Ga of Gallium from a source of Cyclotron-produced Germanium-68. The parent isotope 68Ge has a half-life of 271 days and can be easily sent to hospitals within the generator, where it remains sufficiently active clinically for almost a year. Its decay product68Ga (with a half-life of only 68 minutes, inconvenient for transport) is eluted as the tri-chloride and is finding increasing applications in labelling clinically useful biological markers for Positron Emission Tomography (PET) imaging.   Although there is an initial high cost for the generator, the availability of the daughter product, fresh, several times per day, makes the individual patient dose cost very low. There is growing interest in making Galligasvia a commercial Technegas generator 1, but as the machine is only designed for the lower gamma energy of99mTc, doing so is outside the normal radiation protection guidelines.

Inhalation only ‘Hot Spot’ imaging for Pulmonary Embolism using PET with 68GaCl3

Introduction

In 1977, the 'Father' of PE diagnosis in Nuclear Medicine, George V. Taplin, used a new PET tracer 15O2 labelled CO2 and a Pertechnetate aerosol to examine experimental PE in dogs2.   The proof of concept was validated for the 15O2 in humans three years later from HW (Bill) Strauss’ Department in Boston3.  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 15O2 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 clinically 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 remain unknown, and indeed Professor Jörg Kotzerke recently reported in a personal e-mail that his attempts some years ago to use 'Pertechnegas' clinically, failed.

This proposal revisits the exciting prospect of a new imaging test for PE, requiring a simple inhalation only of the PET tracer 68GaCl3 followed by two identical image sets about 10 minutes apart, with the first subtracted from the second.   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 since it overcomes any resolution limits through extreme specificity, and to achieve this simply in PE diagnosis would be a major breakthrough.

The Proposal

68GaCl3, as eluted directly from the 68Ge generator dissolved in dilute HCl, directly binds to Transferrin in the blood on iv injection.    If the solution is carefully evaporated to dryness in a platinum crucible, it will be ready for immediate use.   It boils at 201°C.  Rapid heating of the crucible above this temperature in a stream of nitrogen (to reduce the risk of chemical dissociation) will then produce an inhalable gas of 68GaCl3.   A patient would go through a breathing manoeuvre similar to that for Technegas and immediately lie under a PET camera for a set of standard images beginning with a PA coronal.   At a given time later, the image set is repeated, and the first image normalised and subtracted from the second.   Where blood is flowing normally in the pulmonary circulation, the resultant image set will show no activity (negative pixels are set to zero), but where it is pooled, but ventilation is normal, as in PE, a ‘hot spot’ will register.

If this procedure, or a close variant of it, works, it will become the ‘gold standard’ screening test for PE in a very short time.

Please send any outcomes of trials or discussions on the idea to Bill Burch for posting on this site.

References

  1. e.g. Hofman, MS, Beauregard, J-M, Barber, TW, et al., 2011, 68Ga PET/CT Ventilation–Perfusion Imaging for Pulmonary Embolism: A Pilot Study with Comparison to Conventional Scintigraphy. J Nucl Med 52:1513–1519.
  2. Taplin, GV, Chopra, SK, Elam, D., 1977, Imaging experimental pulmonary ischemic lesions after inhalation of a diffusible Radioaerosol: concise communication J Nucl Med 18: 250-254.
  3. Nichols, AB, Bella,r GA et al., 1980,  Detection of Pulmonary Emboli by Positron Imaging of inhaled 15O-labelled Carbon Dioxide  Sem Nucl Med 10: 252-258.

Updated:  23 January 2018/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager