Paper of the month September
Published on: September 1, 2019
Title: Matched-pair comparison of 68Ga-PSMA-11 and 18F-PSMA-1007 PET/CT: frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy
Isabel Rauscher1, Markus Krönke1, Michael König1, Andrei Gafita1, Tobias Maurer2,3, Thomas Horn2, Kilian Schiller4, Wolfgang Weber1, Matthias Eiber1
J Nucl Med. 2019 Jun 28.
Weblinks to article:
This exploratory matched-pair study mainly focuses on pitfalls and different interpretation in 68Ga-PSMA-11 and 18F-PSMA-1007 PET/CT imaging. In this study, 18F-PSMA-1007 PET revealed almost 5-times as many PSMA-ligand positive findings attributed to benign origin (mostly ganglia, unspecific lymph nodes and bone lesions) compared to 68Ga-PSMA-11 PET. Further, detection rate for recurrent prostate cancer (PC) in 18F-PSMA-1007 PET was comparable to 68Ga-PSMA- 11 PET in patients after primary radical prostatectomy: 80.4% for both 68Ga-PSMA-11 and 18F-PSMA-1007 PET/CT, respectively. However, it has to be noted, that despite the matched-pair approach with similar clinical characteristics two different patient populations were compared leading to a potential bias.
The presence of PSMA-ligand positive benign lesions (e.g. in ganglia or healing rib fractures) is known since the introduction of 68Ga-PSMA-11 PET, but has increasingly been documented in case reports/series and review articles in the last years. This study is the first documenting the presence of a substantial higher number of PSMA-ligand positive benign lesions in 18F-PSMA-1007 PET (66.4% vs. 29.2% of all PSMA-positive lesions in 18F-PSMA-1007 vs. 68Ga-PSMA-11, respectively).
The presence of significantly more PSMA- ligand positive benign lesions in 18F-PSMA-1007 PET might be related to the lower positron energy of 18F compared to 68Ga improving spatial resolution in 18F-PSMA-1007 PET and higher signal in 18F-PSMA-1007 PET due to longer half-life and higher injected activities.
In 18F-PSMA-1007 PET, the most prevalent pitfall lesion was non-specific physiological radiotracer uptake in cervical, coeliac, or sacral ganglia (67% vs. 12% prevalence in 18F-PSMA-1007 and 68Ga-PSMA PET, respectively).
The second most common pitfall lesion observed was unspecific uptake in LN (e.g. inguinal, axillary or mediastinal). The reason for PSMA-ligand uptake in histopathologically normal LN is not understood yet. However, immunohistochemistry studies show that PSMA is not only present in tumor-associated tissues, but also in inflammatory-associated neovasculature.
The differentiation between suspicious and unspecific PSMA-ligand uptake in LN is challenging. However, it can often be resolved when looking at the shape and configuration of PSMA-positive lymph nodes on CT images (e.g. oval vs. round configuration, presence of fat hilum) and when reading within the clinical context (e.g. pattern of metastasis in PC, PSA-level, extent of disease). CT also plays an important role in the evaluation of benign PSMA-ligand positive bone lesions. PSMA-ligand uptake in healing bone fracture, degenerative changes or fibrocartilage lesions has been described before.
However, especially in 18F-PSMA-1007 PET, a high number of PSMA-ligand uptake in the bone (mainly ribs) was observed showing no clear correlate on CT images. Based on low to intermediate (not high) uptake and considering the patient history many of those were designated as “unspecific uptake” with PSMA-ligand PET/CT follow-up being available only in a limited number of patients. Notable, free 18F cannot be regarded as a substantial issue for the unspecific PSMA- ligand uptake in the bones as mean free 18F in all patients was only 1.8 ± 1.0%, (range 0-3.6%).
In general, recent studies suggest a higher detection rate of 18F-PSMA-1007 PET compared to 68Ga-PSMA-11 PET due to the higher spatial resolution of 18F and the superior differentiation of ureter/ bladder activity from local recurrence/ locoregional LN metastases with 18F-PSMA-1007. The agent is only minimally excreted via the urinary tract posing a potential advantage.
A considerably higher number of visually detectable findings with increased PSMA-ligand uptake attributed to benign origin is present in 18F-PSMA-1007 PET compared to 68Ga-PSMA-11 PET. Therefore, especially for 18F-PSMA-1007, side-by-side evaluation of PET and CT images as well as sophisticated reader training emphasizing known pitfalls and reporting within the clinical context is obligatory for correct and reliable PSMA-ligand PET/CT interpretation. Detection efficacy of lesions attributed to recurrent PC was comparable in this matched-pair analysis in patients with biochemical recurrence after primary radical prostatectomy.