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

• Published in: European journal of nuclear medicine and molecular imaging 2017-04, Vol.44 (4), p.678-688
• Main Authors: Giesel, Frederik L., Hadaschik, B., Cardinale, J., Radtke, J., Vinsensia, M., Lehnert, W., Kesch, C., Tolstov, Y., Singer, S., Grabe, N., Duensing, S., Schäfer, M., Neels, O. C., Mier, W., Haberkorn, U., Kopka, K., Kratochwil, C.
• Format: Article
• Language: English
• Subjects: Aged; Antigens; Antigens, Surface - metabolism; Cardiology; Dosimetry; Fluorine Radioisotopes; Glutamate Carboxypeptidase II - metabolism; Histopathology; Humans; Imaging; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Positron Emission Tomography Computed Tomography; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - pathology; Radiation; Radiation Dosage; Radiology; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - adverse effects; Radiopharmaceuticals - pharmacokinetics; Renal Elimination; Tissue Distribution; Tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-016-3573-4

Purpose The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68 Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68 Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18 F-labelled analogs. 18 F-PSMA-1007 was selected among several 18 F-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 18 F-PSMA-1007 in human volunteers and patients. Methods Radiation dosimetry of 18 F-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 18 F-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, 18 F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18 F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18 F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to 18 F-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. 18 F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter. Conclusion 18 F-PSMA-1007 performs at least comparably to 68 Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68 Ga-labelled PSMA-targeted tracers.