RESUMEN
PURPOSE: The 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. METHODS: Radiation 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. RESULTS: With 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.
Asunto(s)
Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Dosis de Radiación , Radiofármacos/farmacocinética , Anciano , Radioisótopos de Flúor , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Radiofármacos/administración & dosificación , Radiofármacos/efectos adversos , Eliminación Renal , Distribución TisularAsunto(s)
Proteína BRCA2/genética , Mutación de Línea Germinal , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The ultimate goal of a personalized approach to prostate cancer patient management relies on two prerequisites: the development of preclinical but clinically relevant model systems and robust prognostic and predictive biomarkers. The past several years have shown significant progress towards these two prerequisites which will be highlighted in this review using some notable examples.