In PCa individuals who underwent pretendly curative treatment and who experience biochemical recurrence, identifying where recurrent prostate cancer is located is crucial for planning subsequent treatments [12].

Following the identification of biochemical recurrence (PSA 0. 2 ng/ml), it is crucial to ascertain if it is localized or spread, as this influences the treatment options available, particularly for a specific group of patients who might qualify for curative salvage treatments. Traditional imaging methods like cross-sectional scans or bone scans have a low success rate in identifying these cases, particularly when serum PSA levels are low [13].

As a result, different radioactive markers are being researched to enhance the imaging of both recurring and initial cases of prostate cancer.  So far, PSMA radioligands have emerged as the most accurate and precise for detecting prostate cancer, especially in patients at high risk for the disease [12].

PET/CT with 68Ga-PSMA has been proposed as a promising tracer for imaging patients with biochemical recurrence at low PSA levels with the potential of changing clinical management, performing better than the old gold-standard radiolabelled choline [4].

Also, the indication for detection of metastases for initial staging and its use in theragnosis-concept (¹⁷⁷Lutetium) is rapidly being consolidating [5,10].

However, 68Ga labelled PSMA has several shortcomings such as limited availability for clinical use of the 68Ga generator, non-ideal energies, short half-life and a high urinary excretion, which can obscure detection of the primary or residual disease.

The introduction of ¹⁸F-labelled tracers has demonstrated promising results for the diagnostic workup of prostate cancer and seem to be an attractive alternative to 68Ga-PSMA-11 due to several principal advantages: availability of larger amounts of activity, a lower positron energy, higher image quality and possibility of delayed images.

An interesting tracer developed in our Centre: ¹⁸F-ALF-PSMA-11, can be produced on a large scale with suitable radiochemical purity for clinical purposes.

This tracer has been suggested as a novel and attractive alternative to ⁶⁸Ga-PSMA-11 and others ¹⁸F-PSMA tracers with accessibility and commercial advantages as well as similar tumour uptake among them and the additional advantage of low cost. Notable a recent paper made a head-to-head comparison between ¹⁸F-AlF-PSMA-11and ⁶⁸Ga-PSMA-11, performing in a comparable way [9].

¹⁸F-PSMA-1007 is a novel PSMA ligand that has excellent preclinical characteristics and that is only minimally excreted by the urinary tract, a potential advantage for pelvic imaging.

¹⁸F-PSMA-1007 had demonstrated properties as high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. This is interesting because most published studies investigated the diagnostic potential agents that are excreted renally.

We report the first experience at our center with ¹⁸F-PSMA-1007 identifying its advantages and potential applications and making a prospective comparation with ¹⁸F-ALF-PSMA-11 concerning image quality and diagnostic values of both tracers in a sample of PCa patients at biochemical relapse.

Our team was the first to improve the creation of an Al¹⁸F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand using an automated synthesis system.  This process achieved a good level of radiochemical purity that is acceptable for clinical use, and it also offered the benefit of being affordable [9].

A head-to-head comparison between ¹⁸F-AlF-PSMA-11 and ⁶⁸Ga-PSMA-11 demonstrated good performance of both tracers in diagnosing PCa [14].

In this prospective study were included 18 patients with biochemical recurrent PCa (median age: 69.5, range: 54-80 years; median PSA level: 1.28 ng/mL; range: 0.01-25.4 ng/mL; Gleason Score >6) who were previously treated with radical prostatectomy and/ or radiation therapy of prostate bed (50% each).

There were no side effects in any patient post-injection of the radiotracer.

The normal organ biodistribution of ¹⁸F-PSMA-1007 and ¹⁸F-AlF-PSMA-11 has proven highly similar to other PSMA-targeted radiotracers, such as PSMA-617, DCFBC and DCFPyL [6-8].

Images of both tracers were of high visual quality and most lesions showed high contrast, as show in the literature. In healthy subjects, it has been proven that the blood pool contained mean 12% of the ¹⁸F-PSMA-1007 injected dose at 2 h p.i.  Also, clearance via the urinary tract was minimal and in average only 0.7 % of the injected activity were eliminated in the urine during the 2–4 h interval [8].

Overall detection rate was 83% (15/18) and 72% (13/18) for ¹⁸F-PSMA-1007 and ¹⁸F-AlF-PSMA-11 PET/CT, while distant metastasis was detected in 13 (72%) and 11 (61%) patients respectively.

These data are similar to previous reports concerning this PSMA ligand. In two studies sites of BCR were localized in 90 % of patients including those with modest elevations in prostate specific antigen (PSA) [15,16].

The detection rates for disease for PSA levels <1,28 and >1,28 ng/mL (median PSA of our sample) was 66% and 100% por ¹⁸F-PSMA-1007, and 55% and 88%, for ¹⁸F-AlF-PSMA-11, respectively.

Our findings align with earlier studies regarding these PSMA ligands.

Perera reviewed sixteen studies that included 1309 patients. The positive scan rates for PSA categories 0–0. 2, 0. 2–1, 1–2, and 2 ng/ml were 42%, 58%, 76%, and 95%, respectively. When analyzing by patient, both the overall sensitivity and specificity were found to be 86%. In terms of per-lesion analysis, the overall sensitivity and specificity were 80% and 97%, respectively [17].
Afshar-Oromieh and their team identified at least one prostate cancer-related lesion in 83% of the patients. They showed detection rates of 50% for patients with serum PSA levels at 0. 5 ng/ml and 58% for those with PSA levels between 0. 5 and 1 ng/ml [18].

An aggregated detection rate of 89. 5% was found in a consistent group of 248 patients after they underwent radical prostatectomy. The detection rates for early biochemically recurrent cancer at PSA levels of 0. 2–0. 5 and 0. 5–1 ng/mL were recorded as 57. 9% and 72. 7%, respectively [16].
In an initial study on 68Ga-PSMA-IT, detection rates were noted to be 52% for PSA levels below 0. 5 ng/mL, 55% for levels between 0. 5 and 1. 0 ng/mL, 70% for levels between 1. 0 and 2. 0 ng/mL, and 93% for levels between 2. 0 and 5. 0 ng/mL [19].

Even though there were only a few patients involved, this research supports a strong detection rate for both markers at low PSA levels in a planned trial setup.

A total of 157 lesions were detected by at least one radiopharmaceutical in the following sites: bone (n=120), lymph-nodes (n=20), prostate (n=9), lung (n=7) and brain (n=1); adding a total of 142 for ¹⁸F-PSMA-1007 and 143 for ¹⁸F-AlF-PSMA-11. Discriminating by radiotracer in the total population, PET/CT with ¹⁸F-PSMA-1007 and ¹⁸F-AlF-PSMA-11 identified 105 and 115 bone lesions, 20 and 15 lymph node lesions, 9 and 6 prostate lesions, 7 and 6 lung lesions and 1 brain lesion both, respectively.

In our research, ¹⁸F-PSMA-1007 PET/CT detected lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter.

Giessel and his team were the first to describe that ¹⁸F-PSMA-1007 PET/CT could detect micrometastases in patients with Biochemically Recurrent Prostate Cancer at very low PSA levels providing critical information to correctly restaging disease and to discuss appropriate treatment options [20].

In our sample PET/CT with ¹⁸F-PSMA-1007 and ¹⁸F-AlF-PSMA-11 identified 20 and 15 lymph node lesions, respectively.

The same author demonstrated an excellent sensitivity of 94.7% with ¹⁸F-PSMA-1007 PET/CT in detecting lymph-node metastases in the pelvis, [21] performing better than ⁶⁸Ga-PSMA-PET.(20, 22) This can be explained: as lymph node metastases with median diameters of 5-6 mm are close to the technical resolution limits of PET with 68Ga-PSMA tracers, it would be reasonable that ¹⁸F-PSMA tracers might perform at a higher level.

For concordant lesions (n=127), we did not find a significantly different SUVm for both tracers: 14.8 (2.6-107.4) and 13.7 (2.5-75.3), median (range), for ¹⁸F-PSMA-1007 and ¹⁸F-AlF-PSMA-11, respectively (p=0.13).

However, a significant correlation was found among both tracers’ SUVm (r = 0.94, n = 127, P< 0.00001).

We found a significantly higher SUVm for ¹⁸F-AlF-PSMA-11 in concordant bone lesions (n=100, P<0.0001) and for ¹⁸F-PSMA-1007 in lymph-node concordant lesions (n=14, P=0.011), while no significant differences were found in prostate and soft tissue lesions.

The increased absorption of ¹⁸F-AlF-PSMA-11 in bones can be understood. Lütje proposed that there is a slight instability that leads to Al¹⁸F absorption in bones, which could complicate interpretations and make it hard to see small prostate cancer bone metastases. Furthermore, the significant non-specific absorption in bones injected with ¹⁸F-AlF-PSMA-11 indicated a quick breakdown in living organisms, a finding that was supported by a plasma stability test conducted in a lab. To avoid the major time-related breakdown of 18F-AlF-PSMA-11, PET imaging should occur no later than one hour after injection. In our research, this was not an issue, and we were able to detect metastases using established standard criteria [23,24].

With regard to normal organs the biodistribution of the two tracers differed.

This is consistent with Giesel´s results who demonstrated distinct organ uptake for lacrimal glands, salivary glands, liver, spleen, small intestine and kidneys in healthy volunteers [8].

¹⁸F-AlF-PSMA-11 had renal clearance and ¹⁸F-PSMA-1007 had hepatobiliary clearance.

Statistically, uptake was significantly higher for ¹⁸F-AlF-PSMA-11 than for ¹⁸F-PSMA-1007 in the kidneys (median SUVm, 46.2 vs. 25.9; p=0.0012) and urinary bladder (median SUVm, 71.2 vs. 5.1; p=0.0003), whereas ¹⁸F-PSMA-1007 showed significantly higher uptake in the liver (median SUVm, 17.9 vs. 7.2; p=0.0003) and gallbladder (median SUVm, 22.8 vs. 2.2; p=0.0003). There were no significant differences comparing uptake in the spleen (median SUVm, 18.2 vs. 16.7; p<0.05). ¹⁸F-PSMA-1007 had statistically significant higher uptake in the salivary glands, parotid glands and lacrimal glands (median SUVm, 27.3 vs.17 .0, p=000.4; 17.9 vs 7.2, p=.0.0003 and 13.47 vs 9.9. p=0.0003 respectively).

The SUVmax values of normal organ biodistribution and tumor uptake examined, were similar to those reported in the literature. For example, the delineation of tumors improved at 3 h p.i reached an average SUVmax of 41 in the primary tumors [8].

It has been proben uptake was significantly higher for ¹⁸F-DCFPyL than for ¹⁸FPSMA- 1007 in the kidneys, urinary bladder, and lacrimal gland, hereas ¹⁸F-PSMA-1007 showed significantly higher uptake in the liver, gallbladder, spleen and salivary glands [25].

The ¹⁸F-PSMA-1007 PET/CT scan is effective in identifying recurrent prostate cancer in many patients experiencing biochemical relapse. Even in patients with a low PSA level of 0. 5 ng/ml or less, the chances of finding abnormal results on the ¹⁸F-PSMA-1007 PET/CT scan appears to be quite high, which could greatly influence how we treat this important group of patients.

The ¹⁸F-AlF-PSMA PET/CT method shows promise for assessing individuals with prostate cancer. In the later stages, a lower liver background might make acute liver failure more likely, particularly in the rare instances where liver metastases arise [26].

When we look at other PSMA-targeting PET tracers, the low amount of urine background in ¹⁸F-PSMA-1007 offers greater diagnostic benefits in PET/CT scans for assessing the prostate bed and pelvis in patients with recurrent prostate cancer. ¹⁸F-PSMA-1007 is at least as effective as 68Ga-PSMA-11, but its longer half-life, along with better energy properties and the absence of urinary excretion, helps to address certain practical challenges faced by 68Ga-labelled PSMA-targeted tracers [26].

Recently, researchers discovered that PSMA is present in the new blood vessels of various non-prostate solid tumors, such as cancers of the breast, bladder, colon, and kidney.  This presence can affect the outcomes and change the precision of the method. In our research, one of the criteria for excluding patients was having additional tumors besides prostate cancer [27].

¹⁸F-PSMA-1007 and ALF operate in a way that is comparable to other PSMA-PET agents and also to other PET tracers that are labelled with ¹⁸F.

On a per patient basis the sensitivity and specificity values with their 95% C.I. were 0.93 (CI: 0.68 - 0.99) and 0.66 (95% CI: 0.09-0.99) for ¹⁸F-PSMA-1007; and 0.84 (CI: 0.54 - 0.98) and 0.60 (95% CI: 0.14-0.94) for ¹⁸F-AlF-PSMA-11, respectively.

Recent research has indicated that there can be times when radiolabeled PSMA uptake is higher in rib fractures and also in non-cancerous bone conditions like fibrous dysplasia and Paget's disease. These observations are important to note when presenting PET/CT findings, which is why the existence of non-cancerous diseases was a criterion for excluding cases in our clinical study [27].

While previous studies have mentioned false positives related to uptake in retroperitoneal celiac ganglia, we were able to identify these instances easily in this analysis, so they were not factored into our results [28].

Regarding inaccurate negative results from PET/CT, some researchers have suggested that the effectiveness of PET/CT might be affected by tiny lesions that are 5 mm, which they consider to be the main limitation of the method. In our findings, the tiniest lymph node identified was 7 mm [22].

There are some notable limitations in our study that should be acknowledged.

Due to ethical and practical constraints, we could not confirm individual lesions through histopathology.  Instead, we classified the lesions using imaging techniques and/or clinical follow-up, as many other studies in the literature have also done [22,29].

There are discussions about how androgen deprivation therapy (ADT) influences how often PET/CT scans with 68Ga-PSMA-11 are detected, but evidence indicates that there is a notable connection between ongoing ADT and the chances of obtaining a pathological radiolabeled PSMA PET/CT scan. In cases of hormone-sensitive prostate cancer (HSPC), receiving ADT before treatment can result in reduced PSMA expression, which in turn diminishes the sensitivity of the radiotracer.

In the group of patients we studied, whether they had concurrent or prior ADT did not exclude them based on PSMA expression and tracer uptake, and its impact on the detection rate remains uncertain.

These tracers demonstrated good diagnostic performance similar to other ¹⁸F-labelled PET-tracers and overcame practical limitations of 68Ga-labelled PSMA targeted tracers. Also, their superior ability to detect recurrence missed by conventional imaging will have a significant impact on patient management.