In this study we evaluated the radiation dosimetry, biodistribution and preliminary efficacy of the new tracer, 18F-PSMA-1007.
Compared to other similar agents, the effective dose of
18F-PSMA-1007 PET/CT (4.4–5.5 mSv for 200–250 MBq) was comparable (Table
2). The effective organ half-life and, hence, the exposure, depends primarily on the short physical half-life of
18F rather than the biological half-life of the carrier molecule. All Glu-urea-based PSMA-targeted tracers share a similar physiological tracer distribution, thus the organ ratios differ only minimally among the various ligands. One strength of our dosimetry estimation is that we utilized a large number of ten head-to-toe whole-body scans performed up to 6 h p.i. (i.e. > 3 physical half-lives of
18F) allowing for excellent curve fitting. One source of uncertainty is the limited number of healthy subjects (
n = 3). Nonetheless, since the normal organ biodistribution of
18F-PSMA-1007 has proven highly similar to other PSMA-targeted radiotracers, such as PSMA-11, PSMA-617, DCFBC and DCFPyL [
13,
14,
29,
30], we consider that the results of this first dosimetry study are in keeping with prior results. The performance of dosimetry in normal volunteers is preferred to performing it in patients with large tumor masses as these could cause tumor “sink effects” distorting the normal biodistribution. This has proven to be less of a concern in PSMA ligands such as
18F-DCFPyL, in which it was shown that the dosimetry in normal organs was reliably assessed independently of the presence of tumor [
14].
The average 1 h and 3 h SUV
max of
18F-PSMA-1007 in tumor tissue, parotid glands, liver, kidneys and spleen can be compared to data for PSMA-11 [
9,
29] and PSMA-617 [
30], because the evaluation of these
68Ga-labelled PSMA-ligands were also performed at our institution with similar imaging protocols, cross-calibrated scanners and analysis software. In contrast,
18F-DCFBC and
18F-DCFPyL have been evaluated with different scanners and imaging protocols which makes the comparison less accurate. However, even the comparison with PSMA-11 and PSMA-617 has limitations. The low patient numbers might introduce errors, especially on the highly variable inter-individual tumor uptake. In addition, due to the higher positron energy and increased spill-out-effects,
68Ga quantification might be systematically underestimated in small lesions. Furthermore, the patient selection differs: PSMA-617 was evaluated in a heterogeneous group of patients [
30], whereas PSMA-11 was evaluated primarily in BCR patients [
29]. In contrast PSMA-1007 is now evaluated in patients with treatment-naive high-risk PCa. Therefore, quantification per SUV should be interpreted cautiously. Semi-quantitatively the ratio tumor-to-parotid is comparable for all tracers. PSMA-617 has the lowest uptake in liver, kidney and spleen, which was a goal when developing theranostic PSMA-ligands for radionuclide therapy. However, as known from
177Lu-PSMA-617 dosimetry [
15], PSMA-617 has slower tumor accumulation than PSMA-11 and is considered suboptimal when used as
68Ga-labelled PET-tracer.
18F-PSMA-1007 shares the slightly slower tracer kinetics of PSMA-617, although this is less crucial due to the longer half-life of
18F in comparison to
68Ga. Due to its structural similarity to PSMA-617, it has been suggested that it could be an ideal diagnostic surrogate for patients considering
177Lu-PSMA-617 therapy [
18]. For a pure diagnostic tracer the slightly higher uptake of
18F-PSMA-1007 in visceral organs is negligible with regard to radiation burden and is also of limited clinical impact as visceral metastases occur late in the course of the disease. More importantly the increased uptake in tumor tissue compared to other tracers improves tumor-to-background ratios making it easier to detect small lymph node metastases. It remains to be seen whether patients with advanced castration-resistant PCa will have higher liver background which may interfere with the detection of metastases in comparison to the actual reference compound
68Ga-PSMA-11. One clear advantage for local staging is that
18F-PSMA-1007 is temporarily retained in the kidney parenchyma. For
18F-PSMA-1007, clearance via the urinary tract was only 1.2 % injected activity during 0–2 h and another 0.7 % 2–4 h p.i.; in comparison, 11 % of
18F-DCFPyl is eliminated during the first 2 h via the urinary tract and another 5 % until 3 h p.i. [
14]. Bladder content of up to SUV
max 40 (
68Ga-PSMA-617) and SUV
max 100 (
68Ga-PSMA-11) has been reported for the
68Ga-containing compounds, respectively [
29‐
32]. In contrast, the content of the urinary bladder was SUV
max 5 for
18F-PSMA-1007 (Fig.
4). Obviously, this agent demonstrates delayed urinary excretion and thus fulfills some of the design criteria for the ideal PSMA-targeted PET tracer. This also explains the lower radiation dose to the urinary bladder wall in comparison to other PSMA-tracers, while kidney dose is comparable (Table
2).
In the evaluation of first patients, the sensitivity of
18F-PSMA-1007 for small lymph node metastases was approximately 95 %. Metastatic nodes as small as 1 mm in diameter were discovered. In a retrospective analysis of patients who received pelvic lymphadenectomy after imaging with a variety of PSMA-targeted tracers, the sensitivity for these very small nodes was limited [
33]. Thus, small lesion detection is a very promising early result for the new compound. However, the mentioned study suffered from several limitations, including a long interval between imaging and surgery or the lack of standardization in regard to imaging protocols and documentation of findings [
33]. Therefore, it cannot be concluded that the higher sensitivity in our cohort is caused solely by the improved tracer. Nevertheless, lymph node metastases with median diameters of 5 mm are close to the technical resolution limits of PET with
68Ga-PSMA tracers and, therefore, it would be reasonable that
18F-PSMA tracers might perform at a higher level.