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 (Eiber et al., 2015; Bailey & Piert, 2017; Einspieler et al., 2017; Hicks et al., 2018; Emmett et al., 2019; Farolfi et al., 2019; Hope et al., 2019; Jilg et al., 2019; Müller et al., 2019), and can be useful for salvage radiotherapy planning (SRT) (Calais et al., 2018), and treatment response assessment (Grubmüller et al., 2019). In a matched-pair analysis the detection rates of recurrent tumours were similar between [68Ga]PSMA-11 and [18F]PSMA-1007 (Kroenke et al., 2019).

[68Ga]PSMA-11 PET can be used for detecting breast cancer and its metastases (Kasoha et al., 2017; Sathekge et al., 2017; Morgenroth et al., 2019), and gliosarcoma (Unterrainer et al., 2017).

Voxel-based analysis of ex vivo samples has shown high agreement between tracer uptake and histopathology (Zamboglou et al., 2016), and lesion SUVmax correlates with immunohistochemically determined PSMA expression (Woythal et al., 2018). 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). Image interpretation must also be standardized (Fanti 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 artefacts (Derlin et al., 2016; Lawhn-Heath et al., 2018).

Internalization rate of PSMA radioligands has been assessed in vitro in PSMA-expressing cell cultures. Internalization of [68Ga]PSMA-11 is relatively slow: Lütje et al (2019) measured ∼10% internalization after 60 min, about the same percentage that was membrane bound.

Analysis

Input function

In PET imaging of the pelvic area, abdominal aorta or iliac arteries are visible in the image and can be used to derive image-derived input function (Sachpekidis et al., 2016a).

Compartmental model

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).

SUV and tumour-to-background ratio

Tumour-to-background ratio (TBR) has been calculated using liver as reference region (Hohberg et al., 2019). With another PSMA radioligand, [18F]DCFPyL, liver uptake was less variable between subjects than the uptake of FDG (Li et al., 2017), supporting its use as reference region. Further, for [18F]DCFPyL, SUV had lower interindividual variance than SUL (SUVLBM) (Li et al., 2017). SUV at 3 h p.i. is significantly higher than 1 h SUV in most lesions, but some lesions were better detected in the PET scan at 1 h (Hohberg et al., 2019). Very early images (5 min p.i.) can help to distinguish between lesions and urinary bladder (Kabasakal et al., 2015).

See also:



References:

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.



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Updated at: 2019-12-10
Created at: 2015-03-25
Written by: Vesa Oikonen, Anne Roivainen