Exploring new molecular imaging concepts of prostate cancer

Prostaatkanker wordt in Nederland jaarlijks bij ongeveer 10.000 patiënten gediagnosticeerd en per jaar overlijden circa 2500 patiënten aan de ziekte. Beeldvormende technieken spelen een sleutelrol in de stadiëring van de ziekte en dragen bij een juiste keuze te maken tussen de beschikbare behandelopties. Nucleair Geneeskundige technieken worden in het bijzonder gebruikt voor het detecteren van uitzaaiingen waarvan lymfekliermetastasen en skeletmetastasen bij prostaatkanker het meest voorkomen. Radiofarmaca met bewezen potentie voor het aantonen van prostaatkankercellen die in dit proefschrift zijn onderzocht betreffen: 99mTc-MDP, 99mTc-HDP, NaF, 11C-choline, 18F-fluorocholine en 18F-DCFPyL. Met behulp van een literatuurstudie en eigen data werd duidelijk dat NaF PET/CT en Choline PET/CT geschikter is voor het aantonen van skeletmetastasen dan scintigrafie met 99mTc-MDP of HDP wat reeds decennia lang gebruikt wordt. Met behulp van Choline of 18F-DCFPyL, kunnen behoudens skeletmetastasen ook uitzaaiingen in wekedelen, zoals lymfklieren gedetecteerd worden. Er werden verschillende aspecten onderzocht die van invloed zouden kunnen zijn op het rendement van deze technieken. Daarbij werd duidelijk dat het van meerwaarde is om een scan te maken direct na toediening van Choline en circa 45 minuten later. Vasten gedurende meerdere uren voor Choline PET/CT heeft geen meerwaarde. Choline PET/CT heeft weinig waarde bij de detectie van de primaire laesie of een recidief in de prostaat zelf. Voor 18F-DCFPyL blijkt een scan 120 minuten na toediening in 39% van gevallen meer afwijkingen te laten zien dan een scan 60 minuten na toediening

Impact of fasting on F-18-fluorocholine gastrointestinal uptake and detection of lymph node metastases in patients with prostate cancer

BACKGROUND: (18)F-fluorocholine PET/CT is used to detect lymph node metastases in prostate cancer patients. Physiological (18)F-fluorocholine in the gastrointestinal tract, especially in the intestines, may interfere with the detection of malignant lymph nodes. Fasting is frequently proposed in literature; however, scientific support is lacking. This study aims to determine the impact of fasting on (18)F-fluorocholine uptake in the gastrointestinal tract. METHODS: Eighty patients were studied, 40 fasted for at least 6 h prior to (18)F-fluorocholine administration while the other 40 did not fast. (18)F-fluorocholine uptake pattern and intensity were evaluated in the intestine near the abdominal aorta and four regions near the iliac arteries. (18)F-fluorocholine intensity was also measured in the liver, pancreas, stomach and spleen. FINDINGS: No statistically significant differences were found in (18)F-fluorocholine uptake in the gastrointestinal tract between the fasting and non-fasting group. CONCLUSIONS: Fasting for 6 h has no effect on (18)F-fluorocholine uptake in the gastrointestinal tract. Therefore, no effects on the detection of malignant lymph nodes are expected, and fasting is not recommended in our opinion

Incidental Findings on 18 F-Fluorocholine PET/CT for Parathyroid Imaging

Introduction   18 F-choline positron emission tomography/computed tomography (PET/CT) is an upcoming imaging technique for the localization of hyperfunctioning parathyroid glands. However, 18 F-choline is a nonspecific tracer that also accumulates in malignancies, inflammatory lesions, and several other benign abnormalities. The aim of this study was to determine the occurrence and relevance of incidental findings on 18 F-choline PET/CT for parathyroid localization. Materials and Methods   18 F-choline PET/CTs performed in our center for parathyroid localization from 2015 to 2019 were reviewed. Abnormal uptake of 18 F-choline, with or without anatomical substrate on the co-registered low-dose CT and also incidental findings on CT without increased 18 F-choline uptake were recorded. Each finding was correlated with follow-up data from the electronic medical records. Results  A total of 388 18 F-choline PET/CTs were reviewed, with 247 incidental findings detected in 226 patients (58%): 82 18 F-choline positive findings with corresponding pathology on CT, 16 without CT substrate, and 149 18 F-choline negative abnormalities on CT. Malignant lesions were detected in 10/388 patients (2.6%). Of all 98 detected 18 F-choline positive lesions, 15 were malignant (15.3%), concerning 4 metastases and 11 primary malignancies: breast carcinoma ( n  = 7), lung carcinoma ( n  = 2), thyroid carcinoma ( n  = 1), and skin melanoma ( n  = 1). Conclusion  Clinically relevant incidental findings were observed in a substantial number of patients. In 15.3% of the incidental 18 F-choline positive findings, the lesions were malignant. These data contribute to better knowledge of 18 F-choline distribution, enhance interpretation of 18 F-choline PET/CT, and guide follow-up of incidental findings. Attention should especially be paid to breast lesions in this particular patient group with hyperparathyroidism in which women are typically over-represented

(18)F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution

There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For Ga-68-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For (18)F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of (18)F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer.  Methods: Images were acquired 60 and 120 min after injection of (18)F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points.  Results: Our data showed a significantly increasing uptake of (18)F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P <0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-tonoise ratio of 11.93 was found for images acquired 120 min after injection (P <0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15).  Conclusion: (18)F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for (18)F-DCFPyL

Early response evaluation of PD-1 blockade in NSCLC patients through FDG-PET-CT and T cell profiling of tumor-draining lymph nodes

ABSTRACTBetter biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation using Fluor-18-deoxyglucose positron emission tomography and pre- and on-treatment flowcytometric T-cell profiling in peripheral blood and tumor-draining lymph nodes (TDLN). The on-treatment evaluation was performed 7–14 days after the start of PD-1 blockade in NSCLC patients. These data were related to (pathological) tumor response, progression-free survival, and overall survival (OS). We found that increases in total lesion glycolysis (TLG) had a strong reverse correlation with OS (r = −0.93, p = 0.022). Additionally, responders showed decreased progressors and increased Treg frequencies on-treatment. Frequencies of detectable PD-1-expressing CD8+ T cells decreased in responders but remained stable in progressors. This was especially found in the TDLN. Changes in activated Treg rates in TDLN were strongly but, due to low numbers of data points, non-significantly correlated with ΔTLG and reversely correlated with OS

(18)F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes:Detection Rate, Image Quality, Activity Kinetics, and Biodistribution

There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For Ga-68-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For (18)F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of (18)F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer.  Methods: Images were acquired 60 and 120 min after injection of (18)F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points.  Results: Our data showed a significantly increasing uptake of (18)F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P <0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-tonoise ratio of 11.93 was found for images acquired 120 min after injection (P <0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15).  Conclusion: (18)F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for (18)F-DCFPyL

18F-DCFPyL PET/CT in primary staging of prostate cancer

Abstract Background Correct primary staging is mandatory for therapy selection and to determine prognosis in prostate cancer patients. Commonly used diagnostic procedures including Computed Tomography (CT), Magnetic Resonance Imaging, Choline Positron Emission Tomography/Computed Tomography (PET/CT) and extended lymph node dissection (ePLND) have suboptimal diagnostic accuracy for primary staging. PSMA targeting radiopharmaceuticals have shown better diagnostic accuracy than commonly used imaging procedures. This study presents data of a retrospective cohort of patients that received PET/CT with 18F-DCFPyL for staging of primary prostate cancer. Methods From November 2016 until April 1018 all consecutive patients that received 18F-DCFPyL PET/CT for primary staging of prostate cancer were included in the study. 18F-DCFPyL PET findings in the primary tumour were scored. Detection rates of metastases were calculated for different clinical parameters, including PSA, Gleason score, clinical T-stage and risk on having lymph node metastases according to established prediction models. Subsequently, for lymph nodes, 18F-DCFPyL PET findings were compared to morphological features on the co-registered contrast enhanced CT and, for patients with risk on lymph node metastases > 5% according to prediction models, it was scored whether 18F-DCFPyL positive lymph nodes were present at locations that would be resected during ePLND, as well as presence of positive nodes or other metastases outside this area. Results One hundred thirty-three patients were analysed. Increased 18F-DCFPyL uptake the in primary tumour was found in 98% of the patients. In 69 patients increased 18F-DCFPyL uptake was found in lymph nodes, of which 48 and 45% had unsuspicious morphological characteristics on CT (size cut-off ≤6 mm short axis), for locoregional and distant nodes, respectively. In 43% of patients 18F-DCFPyL PET/CT detected lesions suspicious for metastases outside the ePLND area. 18F-DCFPyL PET/CT detection rates are in line with established prediction models of risk on lymph node metastases. Conclusion 18F-DCFPyL PET/CT shows more lymph nodes with pathological characteristics as compared to the co-registered contrast enhanced CT alone. 18F-DCFPyL PET/CT detects lesions suspicious for metastases outside the ePLND area in 43% of patients, with risk on lymph node metastases exceeding 5%, which therefore may be excluded for ePLND. 18F-DCFPyL PET/CT detection rates are in line with established prediction models of risk on lymph node metastases. Large prospective trials that compare 18F-DCFPyL findings with histopathological findings after ePLND are needed in order elucidate sensitivity of 18F-DCFPyL PET/CT and to position 18F-DCFPyL PET/CT in the staging algorithm for primary prostate cancer

(99m)Tc-HDP bone scintigraphy and (18)F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer

INTRODUCTION/AIM: Correct staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with (99m)Tc-phosphonates (BS) is generally advised for staging by guidelines in high risk prostate cancer, this imaging technique is hampered by a high rate of inconclusive results and moderate accuracy. Potentially better imaging techniques for detection of bone metastases such as (18)F-sodiumfluoride PET/CT (NaF PET/CT) are therefore being evaluated. In this observational cohort study we evaluate the performance and clinical impact of both BS and NaF PET/CT in primary staging of patients with prostate cancer. METHODS: The first of two cohorts consisted of patients who received a BS while the second included patients who received a NaF PET/CT for primary staging of prostate cancer. For both cohorts the number of positive, negative and equivocal findings, calculated diagnostic performance of the imaging modality in terms of sensitivity and specificity, as well as the impact on clinical management were studied. The ranges of the diagnostic performance were calculated both assuming that equivocal findings were positive and assuming that they were negative for bone metastases. For the NaF PET/CT cohort the number of patients with signs of lymph node metastases on low dose CT were also recorded, including the impact of these findings on clinical management. RESULTS: One-hundred-and-four patients underwent NaF PET/CT, whereas 122 patients underwent BS. Sensitivities of 97-100 and 84-95% and specificities of 98-100 and 72-100% were found on a patient basis for detection of bone metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted further diagnostic procedures in 2% of the patients in the NaF cohort and in 16% in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in 50% of the included patients, of which 25% showed evidence of lymph node metastases only. CONCLUSION: Our data indicate better diagnostic performance of NaF PET/CT compared to BS for detection of bone metastases in primary staging of prostate cancer patients. Less equivocal findings are encountered with NaF PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node metastases are encountered frequently