Background
Current clinical and scientific evidence for 68Ga-PSMA ligand PET/CT and potential indications
Benefit using 68Ga-PSMA ligand PET/CT | Patient group |
---|---|
High estimated benefit/diagnostic gain | • Primary staging in high-risk disease according to D’Amico classification • Biochemical recurrence with low PSA-values (0.2 ng/ml to 10 ng/ml)a
|
Low estimated benefit/diagnostic gain | • Primary staging in low-risk (and intermediate-risk) disease according to D’Amico classification |
Potential application with promising preliminary data | • Biopsy targeting after previous negative biopsy, but high suspicion of PC (esp. in combination with multiparametric MRI using PET/MRI) |
Potential application with current lack of published data | • Monitoring of systemic treatment in metastatic CRPCb
• Monitoring of systemic treatment in metastatic castration-sensitive PCb
• Active surveillance (esp. in combination with multiparametric MRI using PET/MRI) • Treatment monitoring in metastatic castration-resistant PC undergoing radioligand therapy targeting PSMA (e.g. 177Lu-PSMA-ligand) |
Synthesis, application and imaging protocol of 68Ga-PSMA ligand PET/CT
Display of images
Pattern recognition tips/common variants and artefacts
-
A physiological variable PSMA-ligand uptake can be observed in the following tissues: lacrimal gland, parotid gland, submandibular gland, liver, spleen, small intestine, colon and kidney as seen in Fig. 1. Within healthy organs, kidneys and the urinary collection system including the urinary bladder as well as salivary glands are showing the highest radiotracer uptake. However, especially in localizations where PC metastases mostly occur-the retroperitoneal fatty tissue, benign lymphatic as well as bone tissue-hardly any uptake is noted [33]. Care should be taken in heavily metastasized patients as here visceral metastases can occur. Due to high background activity in the liver potential liver metastases can be obscured. In addition, in advanced disease especially liver metastases tend to loose PSMA-expression—most likely due to de-differentiation. Therefore, in advanced disease the diagnostic CT scan is the mainstay for detection of liver metastases.×
-
For 68Ga-PSMA ligand PET interpretation, first all PET positive lesions suspicious for PC are noted. In PET any focal uptake of 68Ga-PSMA ligand higher than the surrounding background and not associated with physiological uptake has to be considered suspicious for malignancy and judged and described below. As 68Ga-PSMA ligands are excreted via the kidneys and are highly accumulated in the urinary bladder, small local recurrences might be missed. Therefore it is especially important to evaluate PET images in axial as well as coronal and sagittal planes and to change the SUV-threshold to judge the PSMA-ligand uptake in soft-tissue structures near the urinary bladder. Examples of PC patients undergoing 68Ga-PSMA ligand PET/CT examination for primary staging and restaging are presented in Figs. 2 and 3.××
-
Finally, it has to be noted that not all PC exhibit a significant PSMA overexpression. In a study of Maurer et al. about 8 % of patients with primary PC did not show PSMA overexpression—with currently no specific biological explanation [16]. Therefore, correct and careful interpretation of the diagnostic CT scan as part of the 68Ga-PSMA ligand PET/CT examination is of special importance.
-
As 68Ga-PSMA ligand PET/CT imaging is a relatively new imaging technique it is important to be aware that 68Ga-PSMA ligands are not completely specific for PC to avoid scan misinterpretation. So far, several case reports exist showing increased PSMA uptake in benign lesions such as thyroid adenoma, Paget’s disease, schwannoma, tuberculosis, adrenal adenoma or splenic sarcoidosis [22, 34‐36]. Further, it is known that coeliac ganglia show a relevant 68Ga-PSMA uptake. In a study of Krohn et al. at least one ganglion with tracer uptake was found in 76/85 patients (89.4 %) undergoing 68Ga-PSMA ligand PET/CT examination which may mimic lymph node metastases in this area [37]. An example of a 68Ga-PSMA ligand PET/CT examination with focal uptake in the coeliac ganglion is presented in Fig. 4. Interestingly, PSMA expression has also been reported in the tumor neovasculature of some solid tumors (e.g. colon, breast, renal) and in newly formed blood vessels. Apart from PC, other malignant lesions presenting with increased PSMA expression have been reported for glioblastoma, hepatocellular carcinoma, lung cancer, renal cell carcinoma and thyroid cancer [38‐42]. For example, differentiation between lung metastases and primary lung cancer which can also occur in elderly patients as secondary malignancy is a common clinical question. A study by Pyka et al. revealed that quantitative (SUV) analysis of 68Ga-PSMA ligand PET was not able to discriminate reliably between pulmonary metastases and primary lung cancer in PC patients as primary lung cancer lesions can also show high PSMA-expression by 68Ga-PSMA ligand PET. [41]. In summary, in unclear 68Ga-PSMA ligand PET positive lesions, morphological correlation, further clarification with other imaging techniques such as MRI, ultrasound or biopsy is mandatory.×
Formulating reports
Clinical Notes:
In patients with primary PC the following information should be included: |
– date of diagnosis |
– type of verification of diagnosis (biopsy results, time of biopsy, Gleason score) |
– current PSA value |
– previous imaging results |
– relevant further diagnoses (e.g. renal insufficiency, other malignancies) |
In patients with biochemical recurrence additional information is necessary: |
– previous surgery and therapy (e.g. antihormonal treatment, radiation therapy, chemotherapy) |
– initial PSA value, PSA nadir, facultative information on PSA-kinetics |
Technical Details:
|
– exact name of the radiopharmaceutical agent and applied activity, time of scan start post injection, number of bed positions and time per bed position, body weight |
– Information concerning medication administered as preparation of the PET scan (e.g. furosemide) |
– CT-protocol: low-dose or/and diagnostic CT, contrast agent application (oral/rectal/ intravenous, information on concentrations and volumes, native, arterial, portalvenous), scanned portion of the body |