Feasibility of late acquisition [68Ga]Ga-PSMA-11 PET/CT using a long axial field-of-view PET/CT scanner for the diagnosis of recurrent prostate cancer—first clinical experiences

Recently introduced long axial field-of-view (LAFOV) PET/CT scanners offer significant improvements over previous standard axial FOV (SAFOV) systems [1, 2], with substantially improved sensitivity and count densities [3]. Most recently, the first Siemens Biograph Vision Quadra system (Siemens Healthineers, Knoxville, TN, USA) with an axial FOV of 106 cm was installed at the Department for Nuclear Medicine, University Hospital Bern, in Switzerland. The performance characteristics of this scanner have been investigated previously in phantom studies [4, 5] and in a clinical setting [6].

PET/CT with PSMA radioligands is the modality of choice for the staging of biochemically recurrent prostate cancer (PC). Typically, when performed with [⁶⁸ Ga]Ga-PSMA-11, imaging is routinely performed at 1 h post injection of radiotracer (p.i.) [7‐9]. However, this choice of imaging time is drawn from the first clinical description of [⁶⁸ Ga]Ga-PSMA-11, and is not based on a systematic evaluation of the optimal imaging time [7, 10]. Acquisition of images at later time points is associated with improved tumour to background (TBR) and lesion detectability [11‐15] and is mentioned in current guidelines [9]. Despite these benefits to later acquisition, limiting factors are encountered: e.g. the short half-life of the radiopharmaceutical (68 min) results in decay at later imaging, and additional scanning can be difficult to integrate into a busy clinical service. This is particularly the case where, as a result of radioisotope decay, longer acquisition times are required to achieve adequate count statistics which can reduce the scanner’s availability for other patients [9]. Pioneering publications with LAFOV scanners report increased dynamic range for LAFOV systems, meaning that radiopharmaceuticals can be followed usefully over more half-lives as a result of the scanner’s higher sensitivity [1]. The aim of this short communication is to report our initial experiences with a LAFOV scanner in late imaging with [⁶⁸ Ga]Ga-PSMA-11, to demonstrate that later acquisition of imaging is feasible and that even improved image quality can be obtained at late imaging when compared to regular acquisitions.

Patient characteristics are shown in Table 1. All patients have PSMA-avid prostate cancer lesions, with a total of 20 pathological lesions detected and analysed. As anticipated, subjective image quality (as rated on a Likert scale) was judged to be highest for the acquisitions at 1 h p.i. (mean 5/5), with only modest reduction in visual quality observed at 4 h p.i (mean 4.2/5, range 4–5) as rated on a 5-point Likert scale.

Later acquisition was associated with higher lesion SUV_peak (mean 13.43 vs. 10.07, p = 0.05; median 8.46 vs. 6.51). Mean TBR was higher at 4 h compared to 1 h (3.41 vs 1.93, p < 0.001; median 1.55 vs. 1.48); data are shown in Fig. 1. SNR was improved at late acquisition (4 h p.i. 33.02 vs. 1 h p.i. 24.80, p = 0.062; median 15.1 vs 14.2), with borderline significance owing to the limited data in this case series. Data are shown in Fig. 2. Example patient images are shown in Fig. 3 and Fig. 4 and additional images in Supplementary Fig. 1 and 2.

This case series indicates that late imaging is feasible with [⁶⁸ Ga]Ga-PSMA-11 without relevant loss of image quality, where the sensitivity gains in a LAFOV PET/CT system result in greater dynamic range, i.e. the greater sensitivity of the scanner allows radiotracers to be followed over more half-lives [1].

The pharmacokinetic behaviour of [⁶⁸ Ga]Ga-PSMA-11 is well known, and the majority of tumour lesions show increasing radiotracer uptake over time [7]. It is therefore beneficial to observe the radiotracer over several half-lives, which can improve lesion visibility, background tissue clearance and TBR [10‐14, 16, 22]. However, dual time point or later imaging is not universally accepted; additional or discretionary imaging can be challenging to integrate into the clinical routines of a busy nuclear medicine department and may require long acquisition times reducing scanner availability. With a mean applied activity for the patients in this report of 192 MBq, after 4 h, less than 17 MBq of the originally applied activity would be available following decay, and in reality even less would be available when considering the biological half-life [7]. With such low amounts of radiopharmaceutical activity remaining, the resultant imaging quality using previous-generation scanners was clinically unacceptable [23]. A standard acquisition using a SAFOV scanner recommended by the guidelines is 2 min/bp, which for a previous generation scanner in continuous bed motion could take up to 16 min (2 min/bp equivalent to 1.1 mm/s table speed [24]). By contrast, the LAFOV scanner is able to capture a 106 cm FOV in a single acquisition, enabling improved acquisition times: for example, a 16 min/bp acquisition, as we performed at 4 h, would be impracticably long when using a SAFOV system. Whereas later acquisition of images can be to the detriment of image quality using SAFOV systems, this is not the case for LAFOV systems. Moreover, these cases demonstrate the ability to achieve a high-quality image after nearly four half-lives had elapsed, i.e. where > 90% of the applied radiopharmaceutical has undergone decay. Although not the aim of this present study, this implies that as alternative to late acquisition, low dose protocols are feasible in LAFOV, for which further dedicated studies are required. Such low-dose protocols are of clinical interest since they might be a method to ameliorate supply bottlenecks for ⁶⁸ Ga [25].

Despite nearly a decade of routine use, the optimal imaging protocol for [⁶⁸ Ga]Ga-PSMA-11 PET/CT remains elusive. Given the improvement in lesion contrast (TBR) and SNR, rather than acquiring images at 1 h p.i., delayed acquisition might be preferable with new-generation LAFOV scanners. We note that later acquisition is recommended for other ¹⁸F-labelled PSMA-radiotracers, such as [¹⁸F]PSMA-1007 where 2 h p.i. is favoured [26] and where 2 h imaging may be valuable for [¹⁸F]DCFPyl [27].

Our short report is limited by the small patient numbers and represents our first experiences in this regard with this new scanner. Although readers were blinded to clinical details and scans were read in randomised order, recall bias cannot be excluded, although this case series does not seek to present a systematic evaluation but rather to demonstrate the feasibility of later image acquisition and imaging quality achievable on a state-of-the-art LAFOV system as a report of first clinical experiences with the first scanner of this type. Although further systematic analyses are required to confirm our findings, we hypothesise that when using LAFOV systems, later acquisitions could be favoured in certain conditions. Future studies should evaluate other imaging time points, such as 2 h or 3 h p.i.

These initial data demonstrate that, when using a LAFOV scanner, not only are late acquisitions feasible with total acquisition times not exceeding those of a routine scan, but that improvements in terms of TBR and SNR are possible.

In this case series, late acquisition in tandem with a LAFOV PET/CT did not result in reduced imaging quality, however improved TBR and SNR at late imaging. High-quality imaging at a time point when nearly four half-lives for the radiotracer had elapsed was possible within clinically acceptable total acquisition times. These data show that later acquisition times for [⁶⁸ Ga]Ga-PSMA-11 may be preferable when performed on LAFOV systems.