18F-Labelled PSMA-1007 shows similarity in structure, biodistribution and tumour uptake to the theragnostic compound PSMA-617

The biochemical and radiological responses to radionuclide therapy with Lu-PSMA-617 targeting prostate-specific membrane antigen (PSMA) make it a promising approach to the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) [1]. However, PSMA-617 has been reported to have slower tumour accumulation and clearance kinetics than PSMA-11, and the latter is still therefore the preferred diagnostic agent when labelled with generator-produced Ga which has a short half-life (68 min) [2]. A PSMAtargeting F-labelled PET tracer could be producedwith higher activity in a cyclotron and the half-life (110 min) would allow both late imaging beyond 1 h after injection and shipping to satellite institutions. However, the structure of the currently most-used F-labelled PSMA tracer, F-DCFPyl, is different from that of PSMA-617, and like PSMA-11 it might be a suboptimal surrogate for stratifying patients according to their suitability for therapy with Lu-PSMA-617 [3]. Based on the scaffold of PSMA-617, the novel compound F-PSMA-1007 was developed. As shown in the image (a, d), PSMA-1007 shares the Glu-urea-Lys motif targeting the catalytic domain of PSMA and the naphthalene-based linker region considered to cotarget the hydrophobic accessory pocket [4], while in the radiolabel-bearing moiety glutamic acids were added to mimic the carboxylic acid groups of the DOTA chelator to retain the polar charge influencing clearance kinetics. The image also shows a patient with mCRPC who was staged using F-PSMA-1007 (b PET 1 h after injection, maximum intensity projection) and treatment with Lu-PSMA617 (c planar scan 24 h after injection, geometric mean). In analogy to the chemical structure, the uptake in tumour and normal organs is very similar with the two compounds. Thus, F-PSMA-1007 and Lu-PSMA-617 seem to be a perfect theragnostic tandem. Due to the preferred physical characteristics of F for PET imaging and the possibility for largescale production in a cyclotron, F-PSMA-1007 is also a promising alternative to Ga-PSMA-11 for diagnostic purposes. However, non-inferior diagnostic accuracy has still to be proven in a larger cohort. * Clemens Kratochwil clemens.kratochwil@med.uni-heidelberg.de