Quantification of [68Ga]PSMA-11 PET
One of most used PET tracers for imaging PSMA expressing tumours is [68Ga]PSMA-11 ([68Ga]PSMA-HBED-CC). This tracer binds to the extracellular domain of PSMA, and is then assumed to be internalized. [68Ga]PSMA-11 is used for initial staging and detecting recurrent prostate cancer (Bailey & Piert, 2017; Hicks et al., 2018), and can be useful for salvage radiotherapy planning (SRT) (Calais et al., 2018).
Voxel-based analysis of ex vivo samples has shown high agreement between tracer uptake and histopathology (Zamboglou et al., 2016). Tumour detection is positively associated with prostate-specific antigen (PSA) and androgen deprivation therapy (ADT) (Afshar-Oromieh et al, 2015). The optimal acquisition protocol and timing remain under debate for [68Ga]PSMA-11 and other PSMA tracers (Afshar-Oromieh et al., 2016a and 2017). Currently, the recommended scan time is 60 min after administration, with acceptable range of 50-100 min (Fendler et al., 2017). Recommended tumour uptake metrics is SUVmax (Fendler et al., 2017).
In healthy subjects, [68Ga]PSMA-11 is taken up in the salivary glands, liver, spleen, small bowel, kidneys, and urinary tract (mainly bladder) (Afshar-Oromieh et al., 2013; Malaspina et al., 2018). It is rapidly cleared from circulation and non-target tissues, and then excreted into urine. High urine concentration may hinder the evaluation of the prostate bed and pelvic lymph nodes (Malaspina et al., 2018). Forced diuresis and delayed PET imaging can markedly improve image quality and reduce scatter artifacts (Derlin et al., 2016; Lawhn-Heath et al., 2018).
Reversible two-tissue compartmental model can be used to analyze tissue time-activity curves (TACs), using plasma TAC as input function. The first tissue compartment represents the free and non-specifically bound tracer in the interstitial space, and the second compartment the tracer bound to PSMA on cell surfaces or the internalized tracer-PSMA complex. Rate constants K1 and k2 reflect the forward and reverse transport between plasma and the first tissue compartment; k3 represents the binding of tracer to PSMA and its internalization, and k4 represents the dissociation of tracer from PSMA and externalization (Sachpekidis et al., 2016a). Vascular volume fraction (VB) is additionally fitted as model parameter (Sachpekidis et al., 2016a). This model is used primary and recurrent prostate cancer, and in bone metastases of prostate cancer (Sachpekidis et al., 2016a, 2016b, 2018).
Sachpekidis C, Eder M, Kopka K, Mier W, Hadaschik BA, Haberkorn U, Dimitrakopoulou-Strauss A. 68Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer. Eur J Nucl Med Mol Imaging 2016a; 43(7): 1288-1299. doi: 10.1007/s00259-015-3302-4.
Sachpekidis C, Kopka K, Eder M, Hadaschik BA, Freitag MT, Pan L, Haberkorn U, Dimitrakopoulou-Strauss A. 68Ga-PSMA-11 dynamic PET/CT imaging in primary prostate cancer. Clin Nucl Med. 2016b; 41(11): e473-e479. doi: 10.1097/RLU.0000000000001349.
Sachpekidis C, Bäumer P, Kopka K, Hadaschik BA, Hohenfellner M, Kopp-Schneider A, Haberkorn U, Dimitrakopoulou-Strauss A. 68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer. Eur J Nucl Med Mol Imaging 2018; 45(6): 904-912. doi: 10.1007/s00259-018-3936-0.
Updated at: 2019-03-21
Created at: 2015-03-25
Written by: Vesa Oikonen, Anne Roivainen