title: Biodistribution of [(68)Ga]PSMA-HBED-CC in Patients with Prostate Cancer: Characterization of Uptake in Normal Organs and Tumour Lesions.
abstract: The aim of this study was to determine the physiological and pathophysiological biodistribution of [(68)Ga]PSMA-HBED-CC (PSMA-11) ([(68)Ga]PSMA) in patients with prostate cancer (PCA) to establish the range of normal uptake in relevant organs and primary prostate tumours, locally recurrent PCA, lymph and bone metastases and other metastatic lesions. Additionally, we aimed to determine a cut-off uptake value for differentiation of primary tumours from normal prostate tissue.
  
  
  
  Overall, [(68)Ga]PSMA positron emission tomography/x-ray computed tomography (PET/CT) of 101 patients (mean age 69.1 years) with PCA was analysed retrospectively. For assessment of tracer biodistribution, maximum standardized uptake values (SUVmax) were calculated for various normal organs, as well as for primary tumours (PT) and/or metastases. Results are presented as median, interquartile range (IQR; 25th quantil-75th quantil) and range (minimum-maximum).
  
  
  
  [(68)Ga]PSMA PET/CT was performed 50 min (range 30-126) after injection of 109 MBq (range 84-158). Regarding biodistribution, highest uptake (median/IQR/range) of the tracer was found in the kidneys (49.6/40.7-57.6/2.7-97.0) followed by the submandibular glands (17.3/13.7-21.2/7.5-30.4), parotid glands (16.1/12.2-19.8/5.5-30.9) and duodenum (13.8/10.5-17.2/5.8-26.9). The best cut-off value for differentiating physiological uptake in the primary tumour from that in the prostate was found to be an SUVmax of 3.2. The median SUVmax in the PT (n = 35), locally recurrent PCA (n = 8), lymph node (n = 166), bone (n = 157) and other metastases (n = 3) were 10.2, 5.9, 6.2, 7.4 and 3.8, respectively. The best cut-off values for differentiating non-pathological uptake in lymph nodes and bones from tumour uptake were found to be SUVmax of 3.2 and 1.9, respectively. Patients with PSA <2 had significantly lower SUVmax in bone metastases as compared to patients with PSA ≥2 (p < 0.01).
  
  
  
  This biodistribution study provided a broad range of uptake data of [(68)Ga]PSMA-11 for normal organs/tissues, primary prostate tumours and metastatic lesions based on a large patient cohort. Both PT and small metastatic lesions were detectable due to their high tracer uptake. Four-times-higher median uptake in PT in comparison to normal prostate stroma resulted in a high diagnostic accuracy that could potentially be used for multimodal image-guided biopsy with dedicated reconstruction software.
authors.affiliation: Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. vikas.prasad@charite.de.
authors.forename: Vikas
authors.identifier: 0000-0003-2010-4117
authors.initials: V
authors.lastname: Prasad
authors.affiliation: Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Ingo G
authors.initials: IG
authors.lastname: Steffen
authors.affiliation: Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Diederichs
authors.affiliation: Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Makowski
authors.affiliation: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wust
authors.affiliation: Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Brenner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes; D006801:Humans; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D017430:Prostate-Specific Antigen / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D012372:ROC Curve; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; C075313:N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid; D004492:Edetic Acid; D017430:Prostate-Specific Antigen
keywords: Biodistribution; Gleason score (GS); Metastases; PET/CT; Prostate cancer; Prostate-specific antigen (PSA); [68Ga]PSMA-11