The biochemical and radiological responses to radionuclide therapy with¹⁷⁷Lu-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-produced⁶⁸Ga which has a short half-life (68 min) [2]. A PSMA-targeting¹⁸F-labelled PET tracer could be produced with 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-used¹⁸F-labelled PSMA tracer,¹⁸F-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 with¹⁷⁷Lu-PSMA-617 [3].

Based on the scaffold of PSMA-617, the novel compound¹⁸F-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 using¹⁸F-PSMA-1007 (b PET 1 h after injection, maximum intensity projection) and treatment with¹⁷⁷Lu-PSMA-617 (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,¹⁸F-PSMA-1007 and¹⁷⁷Lu-PSMA-617 seem to be a perfect theragnostic tandem. Due to the preferred physical characteristics of¹⁸F for PET imaging and the possibility for large-scale production in a cyclotron,¹⁸F-PSMA-1007 is also a promising alternative to⁶⁸Ga-PSMA-11 for diagnostic purposes. However, non-inferior diagnostic accuracy has still to be proven in a larger cohort.