Towards new horizons in brain PET

Abstract

There is an increasing need in routine clinical neuroimaging for simple and accessible methodologies which can reduce examination times but still provide reliable information about the status of the disease. More widespread use of PET technology would be favoured by avoiding the investment and running expenses associated with an onsite cyclotron. The clinical implementation of PET would benefit from cost reductions. The use of isotope generators could potentially allow centres remote from a cyclotron to have access to a wide range of radiopharmaceuticals. The zinc-62/copper-62 (Zn/Cu) generator is a closeto-optimal radionuclide source for labelling chemically diverse ligands. Zn is produced by the nuclear reaction Cu(p,n)Zn with a proton beam of 27.5 MeV, fitting well with on-demand production by a regional medium-energy cyclotron [1–3]. The generator is compact, is easy to produce and ship and is relatively inexpensive, and the eluate is either automatically chelated by thiosemicarbazone complexes (i.e. ATSM and PTSM) [4] or mixed manually [5]. The 9.3-h half-life of Zn limits the use of the generator to a single day, during which up to 20 doses can be produced. Conversely, the 9.7-min half-life of Cu is short enough to offer the opportunity in a single patient to perform sequential studies as well as studies involving dual tracer combinations in which a Cu investigation can be combined with, for example, an F labelled radiopharmaceutical to provide complementary information [5, 6]. The almost exclusive β emission (97%) of Cu impacts positively on the true coincidences and hence on the sensitivity and count rate, giving good counting statistics even for less-sensitive PET cameras. The short physical halflife of Cu and the biodistribution patterns of its thiosemicarbazone complexes result in effective doses (0.36 mSv/ 100 MBq) of the same order as O-water (0.1 mSv/ 100 MBq), which is in the lower range of the most used radiopharmaceuticals (i.e. F-FDG, 1.9 mSv/100 MBq) [7]. On the other hand, the high positron energy of Cu (E βmax=2.93 MeV) results in a large positron range prior to annihilation and consequently to a significant resolution loss (an intrinsic spatial resolution loss of 4.0 mm compared to 0.7 mm for F). This estimated blur could limit the ability of Cu to precisely detect changes in small areas. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging Isozaki et al. [8] report a wellconducted study with highly accurate assessments of haemodynamic status using a minimally invasive and time-effective methodology. They used for the first time in cerebrovascular disease Cu-ATSM, a radiopharmaceutical originally developed for probing hypoxic tissue [9] and recently proven to be effective in imaging tumours [5] and acute stroke [6]. They were able to demonstrate a highly significant relationship between the early phase (first 3 min after injection) uptake of Cu-ATSM and cerebral blood flow images as evaluated by a bolus injection of O-water. Moreover, the ratio between its late phase (last 10 min after injection) and the early phase was significantly correlated with the oxygen extraction fraction as measured by a bolus inhalation of O2. The conclusion was that dynamic PET acquisition with CuATSM provides information about the haemodynamic status of patients with chronic cerebrovascular disease equivalent to M. Pagani (*) Institute of Cognitive Sciences and Technologies, CNR, Via Palestro 32, 00185 Rome, Italy e-mail: marco.pagani@istc.cnr.it