FCH PET-CT may be superior for the early detection (i.e. bone marrow involvement) of metastatic bone disease. In patients with FCH-negative suspicious sclerotic lesions, a second bone-seeking agent (e.g. (18)F fluoride) is recommended. (18)F fluoride PET-CT demonstrated a higher sensitivity than (18)F FCH PET-CT, but the difference was not statistically significant. Furthermore, (18)F fluoride PET could be also negative in highly dense sclerotic lesions, which presumably reflects the effect of treatment. It will be important to clarify in future studies whether these lesions are clinically relevant when compared with metabolically active bone metastases.
We evaluated the potential of 18 F-fluoromethyldimethyl-2-hydroxyethyl-ammonium (FCH) PET/CT in the detection of recurrent disease or distant metastases and correlated its diagnostic accuracy with prostate-specific antigen (PSA) levels in prostate cancer patients with biochemical evidence of recurrence. Furthermore, the influences of androgen deprivation therapy (ADT) and its duration on 18 F-FCH PET were assessed in this study. Methods: This prospective study included 250 prostate cancer patients with PSA relapse who underwent 18 F-FCH PET/CT. At the time of 18 F-FCH PET/CT imaging, the mean PSA level was 46.9 6 314.7 ng/mL and 55.2% (138/250) of patients were receiving ADT. Overall, ADT was performed on 67.2% (168/250) of patients after initial treatment. Imaging was performed on an integrated PET/CT system. Acquisition started 1 min after intravenous injection of 18 F-FCH (4.07 MBq/kg of body weight) with dynamic PET images in the pelvic region during 8 min (1 min/frame) followed by a static semi-wholebody acquisition. The final diagnosis of positive PET lesions was based on histopathology or a consensus of clinical findings, additional imaging, or follow-up imaging modalities. Results: 18 F-FCH PET/CT was able to correctly detect malignant lesions in 74% (185/250) of patients but was negative in 26% (65/250). In 28% of patients, only 1 lesion was detected (69/250); from these, 65.2% (45 patients) had a local recurrence, 18.8% (13 patients) a single lymph node, and 15.9% (11 patients) a solitary bone metastasis. The sensitivity of the 18 F-FCH PET was significantly higher (P 5 0.001) in patients with ongoing ADT (85%; confidence interval, 80%-91%) than in patients without ADT (59.5%; confidence interval, 50%-69%). 18 F-FCH PET sensitivity was 77.5%, 80.7%, 85.2%, and 92.8% for the trigger PSA levels of more than 0.5, 1.0, 2.0, and 4.0 ng/mL, respectively. Scan sensitivity was 33% in patients with a trigger PSA level of less than 0.3 ng/mL and 77% in patients with a trigger PSA level of greater than 0.3 ng/mL, respectively (P 5 0.001). Using a binary logistic regression analysis model, we showed trigger PSA and ADT to be the only significant predictors of positive PET findings. Conclusion:18 F-FCH PET/CT proved its potential as a noninvasive 1-stop diagnostic modality enabling us to correctly detect occult disease in 74% of patients and to differentiate localized from systemic disease. In patients with biochemical recurrence, it also guides to an optimal treatment approach after initial treatment. Trigger PSA and ADT are the 2 significant predictors of 18 F-FCH-positive PET lesions. ADT seems not to impair 18 F-FCH uptake in hormone-refractory prostate cancer patients.
FCH-PET/CT showed promising results for the early detection of bone metastases in prostate cancer patients. We have found that a HU level of above 825 is associated with an absence of FCH uptake. Almost all of the FCH-negative sclerotic lesions were detected in patients who were under hormone therapy, which raises the possibility that these lesions might no longer be viable. However, clarification and the prognostic value of such lesions require further research.
Introduction: Bone and soft tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblast. Therefore, FAP is a promising therapeutic and diagnostic target.Novel radio-labelled FAP-Inhibitors (e.g. 68 Ga-FAPI46) have shown high tumor uptake in positron emission tomography (PET) in sarcoma patients. Here we report endpoints of the FAPI-PET prospective observational trial.Methods: Forty-seven patients with bone or soft tissue sarcomas undergoing clinical 68 Ga-FAPI-PET were eligible for enrollment into the FAPI-PET observational trial. Of these patients, 43 patients also underwent 18 F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of 68 Ga-FAPI-PET uptake intensity and histopathological FAP-expression analyzed with Spearman's r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by two blinded readers.Results: Primary endpoint was met and the association between FAPI-PET uptake intensity and histopathological FAP-expression was significant (Spearman's r = 0.43; p = 0.03). By histopathological validation PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET positive resulting in an SE of 0.96 (95%CI, 0.82-1.00) on a per-patient and 0.94 (95%CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in FAPI-and FDG-PET was 76.6% and 81.4%, respectively.In 8 (18.6%) patients FAPI-PET resulted in an upstaging compared to FDG-PET. FAPI-PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss kappa: primary κ = 0.78; local nodal κ = 0.54; distant nodal κ = 0.91; lung κ = 0.86; bone κ = 0.69 and other κ = 0.65). Clinical management changed in 13 (30%) patients after FAPI-PET.
Conclusion:We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. Further, using blinded reads and independent histopathological validation we report high PPV and sensitivity of FAPI-PET for sarcoma staging.
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