(68)Ga-PSMA-HBED-CC PET/CT: where molecular imaging has an edge over morphological imaging.

Nuclear medicine is currently taking great steps towards gaining a much more prominent role in the care of patients with prostate cancer. Prostate-specific membrane antigen (PSMA) has been a theranostic target of interest in prostate cancer for over two decades and In/Lu antibody-based imaging and therapy have been studied extensively but without gaining widespread clinical acceptance [1–3]. However, since the introduction of novel functional ligands for PSMA such as Glu-urea-Lys-(Ahx)-[Ga(HBED-CC)] (GaPSMA) [4, 5] , PSMA-DKFZ-617 [6–8] or EuKSubkff-Ga-DOTAGA [9], the number of publications on specifically PSMA-targeted imaging has increased exponentially. This shows the extraordinary potential of this approach as a blockbuster modality for nuclear medicine. Ga-PSMA PET/CT is a fine example of theranostic nuclear medicine. The tracer Ga-PSMA is eminently suitable for selection of patients who can be treated with the novel Lu-labelled therapeutic tracer PSMA-DKFZ-617 [6]. Dramatic success has already been observed even in the small initial number of patients with extensively metastasized therapy-refractory prostate cancer metastases treated with this tracer once strong tracer uptake had been established in prior diagnostic Ga-PSMA PET/CT [6, 10]. Therapeutic nuclear medicine therefore now has a truly large new potential patient collective in whom molecular targeted endogenous radiotherapy may play a pivotal role. Furthermore, PSMA is not only expressed strongly by prostate cancer cells, but also in a variety of other normal tissues and solid tumours – mainly in the tumour vasculature [11–18]. This might open the door to nuclear medicine making the long-sought-after inroad into nonthyroid, non-neuroendocrine cancer therapy even though a sustainable multicentre effort has to be initiated to realize this potential. In this issue of the European Journal of Nuclear Medicine andMolecular Imaging, Giesel et al. report a study comparing the performance of Ga-PSMA PET and conventional morphological imaging with CT in 21 patients scanned prior to radiation therapy [19]. Their findings (again) show the strong potential of Ga-PSMAPET/CT.With conventional morphological criteria based on the size of lymph nodes only 22 % of PET-positive lesions were identified as suspicious for malignancy, and only 7 of 14 patients (50 %) identified as having lymph node metastases on PET were also identified as such using CT-based lymph node diameter measurements. Previous studies have shown the high signal-to-background ratio typical of Ga-PSMA PET/CT [18, 20, 21], Giesel et al. now provide further detail on the diagnostic power of this novel imaging modality: the smallest PET-positive lesions had a short-axis diameter of only 2.4 mm. This is hardly greater than the annihilation distance in water for Ga-emitted positrons of 1.7 mm, and thus approaches the lower limit of the physically possible resolution in human PET imaging. It is exactly the setting of patients referred for salvage radiation therapy in which Ga-PSMA PET/CT may prove to be of great value. Currently standard treatment for postoperative elevation of prostate-specific antigen (PSA) levels is radiation therapy of the former prostate region. It is recommended that this therapy is best initiated at PSA levels ≤0.5 ng/ml [22]. It has already been shown that even at such low levels This Editorial Commentary refers to the article http://dx.doi.org/10.1007/ s00259-015-3106-6.