Abstract
Objectives
We record quantitative differences between 18F-prostate specific membrane antigen (18F-PSMA)-1007 and [68Ga]Ga-PSMA-11 positron emission tomography (PET) prostate scans at our centre to investigate if significant differences exist between suspected lesion and lesion/background parameters studied. We also assess the potential impact of such differences on tracer interchangeability when supply is constrained.
Methods
Sixty-one [68Ga]Ga-PSMA-11 and seventy-two 18F-PSMA-1007 patients were analysed in two cohorts, each comprising 200 lesions. Clinical reports were used to determine maximum standard uptake values (SUVmax) was recorded for suspected lesions (T). Similarly, normalisations of mean standardized uptake (SUVmean) and standardized uptake value-peak (SUVpeak) using lean body mass (SUVlbm) and body surface area (SUVbsa) were estimated. SUVmean of liver backgrounds (B) was recorded to estimate T/B ratios. Metabolic tumour volume and total lesion PSMA (TL-PSMA) were investigated as functional volume surrogates. The Mann-Whitney U test was used to identify significant differences between the [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 distributions.
Results
Significant differences were observed for lesion SUVmax (p=0.0004), SUVpeak (p=0.0017), SUVmean (p=0.0007), SUVlbm (p=0.0002), and SUVbsa (p=0.0005) in lesions with higher [68Ga]Ga-PSMA-11 SUV. Similarly, significant differences were observed in liver SUVmax (p<0.0001), SUVpeak (p<0.0001), and SUVmean (p<0.0001), with higher values for 18F-PSMA-1007. T/B (p<0.0001) and TL-PSMA (p=0.0063) also exhibited significantly higher [68Ga]Ga-PSMA-11 values.
Conclusion
Consistent, predictable, and significant differences were observed in 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 PET scans of lesion, liver, volume surrogates, supporting tracer interchangeability for patients with suspected prostate cancer. Our results also support the recent commissioning of PSMA-based PET tracers in England.
Introduction
Prostate cancer is the most frequently diagnosed cancer and the second most common cause of death among males in the United Kingdom (UK) (1). The most widely used positron emission tomography/computed tomography (PET/CT) oncology imaging agent in England is 18F-fluorodeoxyglucose but it has limitations in diagnosing prostate cancer (2). In contrast, prostate specific membrane antigen (PSMA) imaging agents, such as [68Ga]Ga-PSMA and 18F-PSMA, have shown promise in clinical practice (3,4) and in targeted radioligand therapy applications (5). New prostate cancer-targeted PET imaging agents continue to be developed (6,7,8,9) while 99mTc-labelled PSMA ligands for single-photon emission tomography have also been explored for logistical reasons (10).
Availability of PET imaging agents is often limited in the UK, leading to diagnostic delays. Generator-eluted [68Ga]Ga-PSMA-11, with a short half-life (~68 minutes), has been used widely because of its availability. However, 18F-PSMA-1007, with a longer half-life (~110 minutes), offers greater geographic availability. This may address regional supply inequities while receiving substantial clinical support.
Many prostate cancer imaging studies have focused on the efficacy of radiopharmaceuticals using qualitative parameters such as detectability. However, more recent investigations have compared quantitative differences and their potential impact on analyses (11,12). For example, the VISION prostate cancer trial (13,14) incorporates lutetium-177 (177Lu) Lu-PSMA-617 therapy and defines positive lesions as those with lesion-to-liver uptake ratios tumor-to-background (T/B) >1 measured on 68Ga-PSMA-11 PET/CT scans.
However, different biodistribution effects have been identified between 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 uptake in prostate cancer, leading to significant differences in lesion maximum standard uptake values (SUVmax). Increased hepatic excretion results in significantly higher 18F-PSMA-1007 liver mean standardized uptake (SUVmean), and similar significant differences are observed in the blood pool and spleen (4). Caution is therefore advised when the liver is used as a background tissue in T/B ratio estimation and when tracers are interchanged due to supply shortages. Characterising PET/CT quantitative parameters is essential for interpreting the clinical consequences of using different tracers. This highlights the importance of precise quantitative PET investigations (15,16).
In this study, routine clinically referred PET/CT scans using 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 for suspected prostate cancer are characterised. Quantitative differences between radiopharmaceuticals are recorded, and their clinical implications are discussed, particularly when radiopharmaceuticals are interchanged. Ideally, the results of this local quantitative study can support national commissioning approval of PET-PSMA imaging agents. This outcome would reduce waiting lists and enhance clinical workflows for prostate cancer diagnosis and treatment.
Materials and Methods
A total of 61 [68Ga]Ga-PSMA-11 and 72 18F-PSMA-1007 standard-of-care patients were scanned at our centre according to routine referral criteria for clinical indications of suspected prostate cancer. The inclusion criteria comprised all consecutively scanned subjects identified in the PET imaging database. Patients with observed liver lesions were excluded from further analysis.
Subjects were analysed as two separate imaging-agent cohorts, each consisting of 200 suspected lesions, including metastatic sites of disease. Within the [68Ga]Ga-PSMA-11 cohort, the mean ± standard deviation (SD) for weight, body surface area (bsa), lean body mass (lbm), injected activity, and uptake time were 86.1±16.9 kg, 2±0.2 m2, 63.2±6.8 kg, 187.8±23.9 MBq, and 63.3±9.7 min, respectively. The same values in 18F-PSMA-1007 subjects were 83.6±13.6 kg, 2±0.2 m2, 61.4±7.1 kg, 342±42 MBq, and 94.1±8 MBq, respectively.
Images were acquired using a BIOGRAPH mCT-S64 4R PET/CT scanner operating in step-and-shoot mode. Corrections for geometry, randoms, dead time, scatter, and attenuation were applied to the emission data. PET images were reconstructed using ordered-subsets expectation maximization with point-spread-function modeling and time-of-flight, using 2 iterations, 21 subsets, a 200 × 200 matrix, and a 5-mm FWHM Gaussian filter. Non-contrast CT scan parameters were as follows: 120 kVp; 10 mA for the topogram; 120 kVp with modulated mA; pitch of 0.8; and 3-mm CT slices. The scanner adhered to strict QC protocols, received manufacturer-recommended servicing, and was accredited annually under the Guy’s and St Thomas’ PET Core Lab national clinical trial programme.
Finalized clinical reports, created by PET/CT consultant radiologists, were reviewed by experienced PET physicists to identify the location of reported or suspected lesions. Lesion SUVmax, SUVmean, standardized uptake value-peak (SUVpeak), SUVlbm, and SUVbsa normalizations were recorded for each imaging agent. Liver background SUVmean was also noted, and the ratio of suspected lesion SUVmax to liver background SUVmean was calculated to derive T/B ratios. Furthermore, functional volume-based surrogates metabolic tumor volume (MTV) and total lesion PSMA /(TL-PSMA) (i.e., MTV x lesion SUVmean) were compared between the 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 cohorts.
Siemens Syngo.viaTM imaging analysis software, with manual operator control, was used to record SUVs using different normalizations and to estimate MTV and TL-PSMA for each patient. The Shapiro-Wilk normality test in the StatsDirectTM statistical software package indicated that Mann-Whitney analysis should be used to identify significant differences between the distributions of [68Ga]Ga-PSMA-11 and 18F-PSMA-1007. A 95% confidence interval was used, and statistical significance was defined as p<0.05. This study was conducted as an anonymized clinical audit without the need for patient consent.
Results
A total of 133 patients and 400 suspected lesions, identified on 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 PET/CT scans, were analysed. Results are presented in box-and-whisker plots (minimum, first quartile, median, third quartile, maximum), with the mean value denoted by X.
Suspected Lesion SUV
Statistically significant differences were observed in the distributions of SUVmax (p=0.0004), SUVpeak (p=0.0017), and SUVmean (p=0.0007) between [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 (Figure 1). These differences were also observed in SUVlbm (p=0.0002) and SUVbsa (p=0.0005) normalizations. In all cases, [68Ga]Ga-PSMA-11 exhibited higher mean and median values than 18F-PSMA-1007 (Figure 2).
Liver SUV
Liver SUV results showed highly significant differences between the distributions of [68Ga]Ga-PSMA-11 and 18F-PSMA-1007. Specifically, SUVmax (p<0.0001), SUVpeak (p<0.0001), and SUVmean (p<0.0001) were higher for 18F-PSMA-1007 than for [68Ga]Ga-PSMA-11 (Figure 3).
T/B
T/B ratio distributions differed significantly (p<0.0001), with [68Ga]Ga-PSMA-11 exhibiting higher mean and median values than 18F-PSMA-1007 (Figure 4, left two datasets).
MTV
There was no significant difference in MTV distributions between [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 (p>0.05; Figure 4, middle two datasets).
TL-PSMA
Significant differences were found in TL-PSMA distributions (p=0.0063), with [68Ga]Ga-PSMA-11 exhibiting higher median and lower mean values compared to 18F-PSMA-1007 Figure 4 (right 2 datasets).
%COV
Results indicated greater variability in [68Ga]Ga-PSMA-11 distributions than in 18F-PSMA-1007 for suspected lesion SUV (irrespective of normalisation), liver SUVmean, and T/B. However, %COV for 18FPSMA-1007 was higher for remaining liver SUV, MTV, and TL-PSMA volume estimations (Figure 5).
Discussion
Our centre initially used the widely available [68Ga]Ga-PSMA-11 for prostate cancer imaging on PET/CT. However, logistical supply challenges, combined with substantially increased demand for scans led to long national delays in service delivery. As a result, together with others, we introduced 18F-PSMA-1007 to address the backlog, and we now primarily use this imaging agent. The difference in cohort sizes in our study reflected the limited number of 68Ga PSMA patients scanned before the introduction of our 18F-PSMA service. The identical but larger number of lesions selected between tracers was intended to ensure good statistics by maximising the use of the available scan data. Lesions were selected directly from reports. It is recognised that injected activity regimes and uptake times differed between tracers, but each was optimised for service delivery and, accordingly, their differences were significant. Nevertheless, these logistical issues do not impact the efficacy of this study, as the same protocols were used throughout for each tracer and the study was performed on a single machine. Indeed, many centres routinely exchange these imaging agents to optimise service delivery when tracer supply is compromised, taking these considerations into account.
Despite the potential for interchangeability of [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 imaging agents in clinical practice (17), relatively few studies have conducted direct, matched comparisons (18,19). Furthermore, publications often compare different clinical metrics of efficacy (20), including qualitative interpretations. We characterise PSMA uptake of [68Ga]Ga-PSMA-11 and 18F-PSMA-1007, focusing on quantitative SUV, T/B, and volume-surrogate differences when these tracers are interchanged due to supply issues.
Suspected lesion SUV
In this study, significant differences were observed between the two tracers in SUVmax, SUVpeak, SUVmean, SUVlbm, and SUVbsa, with [68Ga]Ga-PSMA-11 showing higher values (Figures 1, 2). However, in a different consecutive-scan PSMA study using 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 (21) with 46 patients, no significant differences were seen in median SUVmax or SUVpeak for suspected prostate, lymph nodes, or metastatic bone disease. Similarly, no significant differences were observed in the median SUVmax between radiopharmaceuticals in another biopsy-proven study of 40 patients (22). Alternatively, in a separate study (17) of 16 patients, the median SUVmax of primary prostate lesions was greater for 18F-PSMA-1007 than for [68Ga]Ga-PSMA-11 (p=0.002).
Differences in results between studies may highlight variability in study design, patient recruitment, disease stage, acquisition protocols, reversibility of kinetics in organs/lesions (23), and various analysis techniques. Therefore, these issues should be considered when comparing studies and drawing conclusions.
Liver SUV
Our results showed that the 18F-PSMA-1007 SUVmean of normal liver background tissue was significantly higher than the corresponding value for [68Ga]Ga-PSMA-11 (Figure 3), and this outcome agreed with other studies (24). As such, interchanging imaging agents would affect T/B ratios when the liver is chosen as the background. Conversely, differences are predictable, and it may be possible to derive a correction factor between interchanged radiopharmaceuticals if patient selection T/B criteria are met.
T/B
Our results (Figure 4) showed that [68Ga]Ga-PSMA-11 exhibited significantly higher mean and median lesion-to-liver ratio values compared with [18F]PSMA-1007, resulting in a [68Ga]Ga-PSMA-11 mean T/B approximately 3 times that of 18F-PSMA-1007.
However, others have noted that when the spleen (21,24,25) is used for background, 18F-PSMA-1007 uptake is much higher than liver 68Ga uptake, and the range is greater for 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 compared with hepatic PSMA uptake. Another study (17) reported that background median SUVmax was greater for 18F-PSMA-1007 than for [68Ga]Ga-PSMA-11 in the gluteus maximus (p=0.001) and in the blood pool (p=0.001). They showed no significant differences in any T/B ratios between imaging agents. Similarly, consideration of these issues is recommended when comparing studies and drawing conclusions, especially regarding patient selection criteria in trials.
This challenge also applies to the VISION prostate cancer trial, in which patients with metastatic castration-resistant prostate cancer received 177Lu-PSMA-617 therapy. One eligibility criterion was a PSMA-positive [68Ga]Ga-PSMA-11 PET/CT scan, defined by a lesion-to-liver uptake ratio >1. In our study, this suggested 150 of the 200 [68Ga]Ga-PSMA-11patients (i.e. 75%) would be eligible ideally if all other criteria were met. Hypothetically, if the VISION study [68Ga]Ga-PSMA-11 patient-selection criterion (T/B >1) were applied to our 18F-PSMA-1007 T/B data, this would imply that 62 of the 200 18F-PSMA-1007 therapy patients (31%) would be eligible. This represents a 59% difference between the tracers at the same [68Ga]Ga-PSMA-11 T/B ratio threshold. However, it is acknowledged that different biodistributions predominate, and that the refined VISION trial therapy eligibility conditions differed from the broader standard-of-care requirements under which scans were acquired here. These differences highlight the need for careful consideration and caution when tracers are interchanged, for example, due to supply issues.
Furthermore, in our study, we observed significant differences in lesion SUV, liver SUV, T/B, and TL-PSMA between tracers, with mean ± SD values presented in Table 1. However, one must exercise caution when making direct comparisons between tracers using such metrics because bias may influence the results. Knowledge of all influencing factors is essential for a fully valid assessment of clinical efficacy, including tumour stage, recurrence, PSA, injected activity, acquisition protocols, image reconstruction techniques, sample size, and treatments, among others. Reviews in this area (26) have shown that [68Ga]Ga-PSMA-11 exhibits high urinary tract excretion and may complicate the diagnosis of small lesions near the prostate bed or bladder. While 18F-PSMA-1007 is dominated by hepatobiliary excretion with potential for improved ability to identify lesions in the pelvic region. Moreover, others have shown that the sensitivity of [68Ga]Ga-PSMA-11 may be slightly lower than that of [18F]PSMA-1007 for detecting small lesions or at very low PSA levels. [68Ga]Ga-PSMA-11 may benefit from a lower false-positive rate in bone and ganglia compared with [18F]PSMA-1007.
Although differences in results are seen in many published studies, and some are contradictory, the consensus is that both tracers exhibit comparable diagnostic performance in the clinical setting. Local validation of equivalence in tracer exchange is highly recommended to ensure that any departure from expectations is understood. Caution is also advised in clinical trials, particularly if patient recruitment is based on retrospective standard-of-care scans involving, for example, the lesion T/B ratio.
MTV and TL-PSMA
In this study, no significant difference was recorded in MTV between tracers. Estimation of MTV arises from a convolution of factors, including the software algorithm used to derive it, lesion SUVmax, lesion homogeneity or heterogeneity, and neighbouring tissue uptake. With this understanding, the MTV was not statistically significant in our case.
The TL-PSMA is estimated as the product of MTV and lesion SUVmean. In our case, the lesion SUVmean was significantly different between tracers. A Higher lesion SUVmean associated with [68Ga]Ga-PSMA-11, compared with 18F-PSMA-1007, likely contributed to this result. Supporting this, another 42-patient study found that a significant difference in TL-PSMA between tracers enabled the prediction of a high Gleason score in favour of 18F-PSMA-1007 (27).
%COV
We presented diverse %COV results across the quantitative parameters investigated, implying the absence of overall superiority of either PSMA imaging agent. In all cases, the %COV for background liver revealed that 18F-PSMA-1007 was higher than [68Ga]Ga-PSMA-11, while for suspected lesions [68Ga]Ga-PSMA-11 was higher than 18F-PSMA-1007; across parameters studied, the %COV for suspected lesions was higher than that for liver. These findings also confirm results reported by others (24).
In summary, for our entire study, we characterised 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 PET PSMA-suspected lesion SUV, background liver SUV, T/B ratios, and %COV at our centre, and demonstrated that quantitative PET measurements are of the same order of magnitude, while quantitative differences are generally consistent and predictable. Our results, obtained using these imaging agents, support their interchangeability during supply shortages and are consistent with other studies, e.g. (4). We also provide further support for the existing evidence base that supports the national regulatory approval of PET PSMA imaging agents, such as 18F-PSMA-1007, in France in 2021 (28). Indeed, NHS England in 2025 recognised this necessity with commissioning policy approval for PSMA PET e.g. [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 in prostate cancer to ameliorate tracer availability challenges (29).
However, important caveats must be considered when exchanging tracers, particularly in applications such as PSMA radioligand therapy (30,31), including more recent [161Tb]Tb-PSMA (32) and [225Ac]Ac-PSMA (33), where patient therapy selection using T/B ratios may be influenced by individual variations in radiopharmaceutical biodistribution, tissue uptake, and, particularly, background selection.
Study Limitations
This was a single-centre retrospective audit in which all suspicious lesions were identified by reporting radiologists as part of standard-of-care practice. We included all suspected prostate cancer referrals and analysed clinically reported suspected lesions to provide a more realistic system-level quantitative characterization, rather than identifying specific tumour types or sites for analysis, because of the possibility of reduced statistical power. Similarly, PSA levels were not included in reports, and were therefore unavailable for this audit. However, the interchange of tracers is vital for many centres to maintain delivery of prostate cancer imaging services throughout the patient pathway, irrespective of PSA levels, because national demand for diagnosis remains very high. Other constraints in this study include the lack of histological confirmation; therefore, we refer to suspected lesions. Patient cohorts received one radiopharmaceutical but not the other, limiting the ability to make a fully matched comparison. Although hepatic lesions were excluded from the analysis, residual bias may remain in cases where clinicians could not visually identify such lesions. However, scans were interpreted by trained radiologists, and experienced PET physicists conducted data analysis to ensure the validity of the findings.
Overall, we believe that we have satisfied the quantitative case for interchange between [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 tracers for routine use in referrals for suspected prostate cancer, and we support national recommendations that advocate PET PSMA.
Conclusion
We characterised significant differences in [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 PET PSMA suspected prostate cancer patients for suspected lesion SUVmax (p=0.0004), SUVpeak (p=0.0017), SUVmean (p=0.0007), SUVlbm (p=0.0002) and SUVbsa (p=0.0005) with higher [68Ga]Ga-PSMA-11 values. Similarly, for background liver, we confirmed higher SUVmax (p<0.0001), SUVpeak (p<0.0001), and SUVmean (p<0.0001) with 18F-PSMA-1007. We also identified significant differences in T/B (p<0.0001) and in TL-PSMA (p=0.0063). Our results favour adopting these PSMA tracers for routine clinical use in PET for prostate cancer and further support the new NHS England commissioning policy.


