False Positive Findings of [18F]PSMA-1007 PET/CT in Patients After Radical Prostatectomy with Undetectable Serum PSA Levels

Abstract

BackgroundPET-CT using prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals labeled with 68Ga or 18F has emerged as the most sensitive staging tool in prostate cancer (PC). Nonetheless, the occurrence of false positive (FP) findings presents a major concern of this approach. In this prospective study, we investigated the frequency and pattern of false-positive findings of [18F]PSMA-1007 PET/CT in patients after radical prostatectomy with undetectable serum PSA levels. Any discrete non-physiological accumulation of [18F]PSMA-1007 in this population is by definition FP.MethodsSeventeen men after radical prostatectomy, whose serum PSA levels were <0.05 ng/mL at 2–24 months after surgery were prospectively recruited. PET/CT was acquired at both 1 and 2 h after injection of [18F]PSMA-1007.FindingsThree studies (18%) were interpreted as completely normal. Thirty-five foci of “non-physiological” uptake were observed in the remaining 14 (82%) patients, including a single skeletal focus in four patients, multiple skeletal foci in five patients and soft tissue uptake in eight, including in a desmoid tumor and in pelvic lymphocele. The SUVmax of all lesions was in the range of 1–7, except for the desmoid tumor which measured 12.7. All foci were visible in both the 1- and the 2 h studies, presenting a minor (<10%), statistically insignificant increase of SUVmax during this time-interval.InterpretationFP [18F]PSMA-1007-avid foci are found in about 80% of patients with undetectable serum PSA levels. Thus, focal uptake of [18F]PSMA-1007 outside its physiological distribution is not a categorical sign of metastasis and can arise from non-specific uptake of the ligand. The interpretation of [18F]PSMA-1007 PET/CT studies should always consider the clinical context, and lesions with SUVmax < 7 are suspicious for FP.

Increased Petrous Bone Uptake on 18F-PSMA-1007 PET/CT Due to Otospongiosis

“…9 Bone is a common site of false-positive findings and constitutes a potential pitfall in 18 F-PSMA-1007 PET/CT as benign conditions can display increased osteoblastic activity (fractures, fibrous dysplasia), as well as nonspecific focal bone lesions seen in the ribs, pelvis, and spine of prostate cancer patients. 7,[10][11][12][13] However, to our knowledge, this is the first reported case of 18 F-PSMA-1007 uptake in otospongiosis. Otospongiosis should be considered in the differential diagnosis of 18 F-PSMA-1007 uptake in the temporal bone, in particular as the prevalence of otospongiosis in the adult White population is approximately 10%.…”

“…Despite its name, PSMA can be expressed in nonprostatic tissues, and tracer uptake has been described in inflammatory/infectious lesions, benign tumors, and in other nonprostatic malignancies 9. Bone is a common site of false-positive findings and constitutes a potential pitfall in 18 F-PSMA-1007 PET/CT as benign conditions can display increased osteoblastic activity (fractures, fibrous dysplasia), as well as nonspecific focal bone lesions seen in the ribs, pelvis, and spine of prostate cancer patients 7,[10][11][12][13]. However, to our knowledge, this is the first reported case of 18 F-PSMA-1007 uptake in otospongiosis.…”

Development of a high‐performance liquid chromatography method for rapid radiochemical purity measurement of [18F]PSMA‐1007, a PET radiopharmaceutical for detection of prostate cancer

“…20 More recent analyses have signalled some caution in the interpretation of potential false-positive findings in [ 18 F] PSMA-1007 PET, for example, in the bone, particularly in the ribs and pelvis. [21][22][23][24] These uptake patterns are not characteristic of free [ 18 F]fluoride in the bone, which is more diffuse and less specific. The uptake of [ 18 F]PSMA-1007 can also be higher than [ 68 Ga]Ga-PSMA-11 in sacral, coeliac and stellate ganglia as well as in benign inguinal nodes.…”

“…There are indeed fine differences in the uptake of [ 18 F]PSMA‐1007 compared to [ 68 Ga]Ga‐PSMA‐11, with [ 18 F]PSMA‐1007 demonstrating less urinary clearance and higher background in the liver 20 . More recent analyses have signalled some caution in the interpretation of potential false‐positive findings in [ 18 F]PSMA‐1007 PET, for example, in the bone, particularly in the ribs and pelvis 21–24 . These uptake patterns are not characteristic of free [ 18 F]fluoride in the bone, which is more diffuse and less specific.…”

Theranostics in prostate cancer

“…In literature, several other malignant tumors like hepatic cell cancer, bladder cancer, renal cell carcinoma, breast cancer, non-small lung cancer, adrenocortical cancer, colon cancer, neuroendocrine tumors, celiac ganglioma, multiple myeloma, atypical meningioma and glioma, central nervous system (CNS) lymphoma, acute lymphocytic leukemia and lymphoma, osteosarcoma, thyroid cancer, melanoma, but also nonmalignancies like hemangiomas, bone disease like Paget's disease and osseous fibrosis or inflammation may be associated with a PSMA expression high enough to be visualized by PSMA PET/CT [15]. Even in patients after radical prostatectomy with a PSA value < 0.05 ng/ml may show false-positive results [16]. Therefore, in unclear findings, additional biopsy is mandatory to rule out secondary malignancies.…”