Al18F-NOTA-octreotide and 18F-SiFAlin-TATE: two ‘new kids on the block’ in somatostatin receptor imaging

Abstract

Since their introduction in clinical routine, somatostatin receptor agonists (SSAs) labelled with the positron-emitting radionuclide gallium-68, collectively referred to as Ga-DOTApeptides, have gradually replaced the use of In-DTPAoctreotide for imaging of the somatostatin receptor (SSTR) in patients with neuro-endocrine tumours (NETs). Apart from the specific advantages of PET over SPECT, such as a higher sensitivity (counts/Bq) and spatial resolution, the higher affinity of Ga-DOTA-peptides for the SSTR-subtype 2, which is the most overexpressed SSTR-subtype in NETs, offers an additional benefit in detecting SSTR-expressing lesions. Indeed, superior performance of Ga-DOTA-peptide-PET was demonstrated by several groups when comparing it head-to-head to In-DTPA-octreotide-SPECT in patients with NETs, with mainly a significantly higher sensitivity in detecting SSTRoverexpressing lesions [1–4]. Although PET-imaging of NETs with Ga-DOTA-peptides is a well-established and validated technique and offers the additional advantage of forming a theranostic twin with Lu-DOTATATE or Y-DOTATOC, which are currently the most frequently used radiopharmaceuticals for peptide receptor radionuclide therapy (PRRT) in these patients, the use of gallium-68 as a radionuclide also has several disadvantages, mainly of logistic nature. Gallium-68 has the theoretical advantage that it can be made available in nuclear medicine departments from a Ge/Ga-generator, thus not requiring a cyclotron. While in the first years, Ge/Ga-generators were mainly found in larger nuclear medicine departments with access to a dedicated radiopharmacy staff that was needed for tracer production, the introduction and very rapid clinical implementation of Ga-PSMA-11 (Ga-HBED-CC) for imaging of patients with prostate cancer since 2014, has made Ge/Ga-generators and production facilities more widely present. Furthermore, newer generation Ge/Ga-generators have received regulatory approval and kit-based labelling approaches to produce Ga-DOTA-peptides, such as SomaKit TOCTM (Advanced Accelerator Applications S.A.) and NETSPOT® (Advanced Accelerator Applications USA), have become available upon approval by the European Medicines Agency and the Food and Drug Administration, respectively. Despite these advances, the overall activity yield per production batch of Ga-labelled compound remains low (capacity of two to four patients per production) and the halflife of gallium-68 is relatively short (68 min), limiting the potential for centralized production and distribution. In the future, some possibilities may be opened up in this field by advances in the cyclotron production of gallium-68. Apart from logistic disadvantages, gallium-68 also has drawbacks based on its physical characteristics, being its relatively high positron energy (Emean = 0.83 MeV) and thus relatively long positron range (Rmean = 3.5 mm), which may result in a suboptimal spatial resolution [5]. For these reasons, the possibilities of using other PET-radionuclides for SSTR imaging should be explored. Among positron-emitting radionuclides, fluorine-18 is the most commonly used radionuclide for clinical PET imaging and offers several advantages over gallium-68: (1) logistic advantages: fluorine-18 can be produced by cyclotrons in large amounts and its longer half-life of 109.8 min allows fluorine-18-labelled tracers to be transported to remote hospitals that do not have a cyclotron on site; (2) physical properties: fluorine-18 has a low positron energy (Emean = 0.25 MeV) and therefore shorter positron range (Rmean = 0.6 mm), offering higher intrinsic spatial resolution [5]. Similarly to PET imaging of prostate specific membrane antigen (PSMA) in prostate cancer, where F-labelled compounds, such as F-PSMA-1007 [6, 7], have been developed This article is part of the Topical Collection on Editorial