F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients

Abstract

PurposeThe prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18F-labelled analogs. 18F-PSMA-1007 was selected among several 18F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of 18F-PSMA-1007 in human volunteers and patients.MethodsRadiation dosimetry of 18F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent 18F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining.ResultsWith an effective dose of approximately 4.4–5.5 mSv per 200–250 MBq examination, 18F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to 18F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2–3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. 18F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter.Conclusion 18F-PSMA-1007 performs at least comparably to 68Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68Ga-labelled PSMA-targeted tracers.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3573-4) contains supplementary material, which is available to authorized users.

PSMA Ligands for PET Imaging of Prostate Cancer

“…Limited preliminary data indicate that 18 F-PSMA 1007 might have reduced urinary clearance within the first 2 h after injection, potentially allowing for improved assessment of the prostate within this time window (33).…”

“…The most widely used 68 Ga-labeled PSMA ligands for PET imaging are 68 Ga-PSMA-11 ( 68 Ga-PSMA-HBED-CC) and the theranostic agents 68 Ga-PSMA-617 and 68 Ga-PSMA-I&T (28,29). 18 F-labeled agents include 18 F-DCFBC (30,31), 18 F-DCFPyL (32), and 18 F-PSMA 1007 (33). They exploit the average lower positron range (reducing blurring effects), longer half-life, and potential for centralized production and distribution of 18 F compared with 68 Ga. A tabular overview of the most common PSMA ligands in clinical use was recently published (34).…”

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates

“…Obviously, besides target expression, also other factors of tumour biology are present which determine therapy response. This observation and the advent of novel PSMA ligands for potential therapy selection, in particular 18 F ligands [34,35], call for more prospective clinical studies to provide the optimal tools for selection of patients, which may benefit most from targeted radionuclide therapy with PSMA ligands.…”

Reply: PSMA Ligands for Imaging Prostate Cancer: Alternative Labeling by Complex Formation with Al18F2+

“…We also gratefully acknowledge their comments on our articles (1,2) questioning the need for radiofluorinated PSMA PET tracers in addition to the 68 Ga-labeled versions already available as a diagnostic version of theranostic ligands, and we appreciate their perspective on 18 F-labeled PSMA tracers. Indeed, in recent years several 18 F-labeled PSMA radioligands apart from the mentioned 18 F-AlF 21 -labeled variants have already been introduced both preclinically and clinically (3)(4)(5). Particularly, Szabo et al (4) clinically introduced 18 F-DCFPyL, an improved second-generation 18 F-PSMA ligand, which was followed by the work of further optimized next-generation PET tracer 18 F-PSMA-1007 recently introduced by Giesel et al (5).…”

“…Indeed, in recent years several 18 F-labeled PSMA radioligands apart from the mentioned 18 F-AlF 21 -labeled variants have already been introduced both preclinically and clinically (3)(4)(5). Particularly, Szabo et al (4) clinically introduced 18 F-DCFPyL, an improved second-generation 18 F-PSMA ligand, which was followed by the work of further optimized next-generation PET tracer 18 F-PSMA-1007 recently introduced by Giesel et al (5). Both 18 F-labeled ligands have already entered prospective clinical trials, highlighting the obvious high potential of these radiofluorinated tracers for the primary diagnosis of prostate cancer and detection of relapse by means of PET/CT and PET/MRI.…”