# [18F]PSMA-1007

[18F]PSMA-1007 has been developed on the scaffold of a theranostic ligand PSMA-617 (Giesel et al., 2016). It can be used for imaging PSMA expressing tumours, mainly primary and metastatic prostate cancer, but also non-prostate cancers due to PSMA expression in the neovasculature. Diagnostic performance of [18F]PSMA-1007 PET in detection of primary distant metastasis in high-risk prostate cancer is superior to conventional CT and bone scintigraphy, and whole-body MR DWI (Anttinen et al., 2020).

Good tumour-to-background ratios in primary and recurring prostate cancer can be observed 2-3 h after [18F]PSMA-1007 administration (Giesel et al., 2017 and 2018a; Kesch et al., 2017; Rahbar et al., 2018a). Visual analysis of images obtained ∼90 min after administration provided high detection rates for biochemical recurrence of prostate cancer (Giesel et al., 2019; Witkowska-Patena et al., 2019 and 2020).

[18F]PSMA-1007 has shown comparable performance to [68Ga]PSMA-11 and [18F]DCFPyL (Giesel et al., 2018b; Kroenke et al., 2019; Hoberück et al., 2021). In contrast to [68Ga]PSMA-11, [18F]DCFPyL, and several other PSMA radioligands, the slightly more lipophilic [18F]PSMA-1007 is mainly excreted via the hepatobiliary route (Giesel et al., 2017), which reduces the activity in the urinary tract, but leads to higher uptake in the liver, gallbladder, and intestine. Thus, [18F]PSMA-1007 is better for detection of small lesions along the urinary tract, but regions with benign uptake (ganglia, lymph nodes, bone) can be frequently misinterpreted as metastases (Dietlein et al., 2020; Rauscher et al., 2020; Grünig et al., 2021).

The kinetics of [18F]PSMA-1007 may be slower than with [68Ga]PSMA-11, and therefore a later scan time than 60 min has been recommended (Rahbar et al., 2018b). Yet, in a pilot study, comparable performance in prostate cancer staging was obtained already when [18F]PSMA-1007 was started at 60 min after administration (Kuten et al., 2020). Scan time and duration affect the noise level, and image reconstruction parameters need to be adjusted accordingly (Trägårdh et al., 2020).

## Analysis

Diagnostic PSMA PET is usually conducted with static whole-body imaging and interpreted visually. The image voxel values from the static late scan can be converted to standardized uptake values (SUVs), or lesion-to-reference tissue ratio can be calculated, to allow interindividual comparison of the uptake. Image-derived blood pool or muscle is often used as the reference tissue, unless healthy tissue (such as bone marrow) is easily detectable as a reference for lesions in the same tissue type.

### 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., 2020).

### Compartmental model

In vitro studies have shown that the internalized fraction of [18F]PSMA-1007 is markedly higher than with most PSMA radioligands (Cardinale et al., 2017).

Reversible two-tissue compartmental model can be used to analyze tissue time-activity curves (TACs), using plasma TAC or image-derived blood TAC as the 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., 2020). Vascular volume fraction (VB) is additionally fitted as model parameter (Sachpekidis et al., 2020). With 60-min dynamic PET scan, the estimated K1 was 0.11±0.08, k3 was 0.17±0.09, and Ki was 0.05±0.02 min-1 in prostate cancer lesions; 0.18±0.12, 0.26±0.14, and 0.09±0.05 in lymph node metastases; and 0.09±0.08, 0.15±0.08, and 0.04±0.02 in bone metastases; median k3 was 35-fold higher than k4 in prostate cancer lesions (Sachpekidis et al., 2020).

### Mass effect

To obtain good image quality, a certain radioactivity dose must be administered, but if molar activity of the radiopharmaceutical is low, the mass of the ligand may cause saturation of the receptors, especially when small animals are being studied.

With [18F]PSMA-1007, higher mass led to markedly lower uptake mouse xenograft models of prostate cancer, with even higher reduction in salivary glands with low expression of PSMA (Soeda et al., 2019).