Maurits Wondergem

(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 68Ga-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 18F-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 18F-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 18F-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 18F-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-to-noise 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: 18F-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 18F-DCFPyL.

Incidental extra-cardiac findings on 13N-ammonia myocardial perfusion PET/CT

BackgroundThe objective of this study was to describe the prevalence of incidental extra-cardiac findings (IECFs) on myocardial perfusion PET/CTs and the prevalence of potentially clinically relevant and clinically irrelevant IECFs, as well as detection rate of previously unknown malignancies.Methods and ResultsFrom September 2013 until February 2016, a total of 1397 consecutive patients referred for the evaluation of possible ischemia by 13NH3 PET/CT were prospectively included in a database. IECFs were categorized into three groups: potentially clinically relevant IECFs, IECFs that could potentially cause chest pain, and clinically irrelevant IECFs. Additionally, the prevalence of previously unknown malignancies was determined. In 717 (51%) of these patients, 775 IECFs were reported and 115 IECFs were categorized as potentially clinically relevant in 109 (8%) patients. A total of 145 IECFs that could potentially cause chest pain were detected in 139 (10%) patients and 515 clinically irrelevant IECFs were detected in 469 (34%) of the patients. An unknown primary malignancy was histologically proven in 19 patients (1.4%).ConclusionsIECFs are detected on myocardial perfusion PET/CT in approximately half of the patients. In the present study, IECFs were potentially clinically relevant in 8% of the patients and in 1.4% an unknown malignancy was found, most of which were lung cancers.Spanish AbstractAntecedentesEl objetivo de este estudio fue describir la prevalencia de los hallazgos incidentales extra cardiacos (HIECs) en el estudio de PET/CT de perfusión miocárdica y la prevalencia de los HIECs clínicamente relevantes y clínicamente irrelevantes, así como la tasa de detección de patología maligna previamente desconocida.Métodos y ResultadosDe Septiembre 2013 a Febrero 2016, un total de 1397 pacientes consecutivos referidos para la evaluación de posible isquemia con PET/CT con 13NH3 fuero incluidos de manera prospectiva en una base de datos. Los HIECs fueron categorizados en 3 grupos: HIECs clínicamente relevantes, HIECs que potencialmente pudieran causar dolor torácico, y HIECs clínicamente irrelevantes. Adicionalmente, la prevalencia de patología maligna previamente desconocida fue determinada. En 717 (51%) de estos pacientes 775 HIECs fueron reportados y 115 HIECs fueron categorizados como clínicamente relevantes en 109 (8%) pacientes. Un total de 145 HIECs que potencialmente pudieran causar dolor torácico fueron detectados en 139 (10%) pacientes y 515 HIECs clínicamente irrelevantes fueron detetados en 469 (34%) de los pacientes. Enfermedad maligna primaria desconocida fue histológicamente demostrada en 19 pacientes (1.4%).ConclusionesLos HIECs son detectados en el estudio PET/CT de perfusión miocárdica en aproximadamente la mitad de los pacientes. En el presente estudio, los HIECs fueron clínicamente relevantes en 8% de los pacientes y en el 1.4% se encontró enfermedad maligna primaria desconocida, en su mayoría fueron cáncer de pulmón.Chinese Abstract背景本文旨在探讨心肌灌注PET/CTs心脏外发现(IECFs)的检出率,包括潜在临床相关、非潜在临床相关的IECFs,以及未知恶性肿瘤。方法和结果从2013年9月到2016年2月,前瞻性地纳入1397名疑似心肌缺血并接受 13NH3 PET/CT检查的患者。将IECFs分为三组:潜在临床相关的IECFs、可能引起胸痛的IECFs和非潜在临床相关的IECFs。此外,未知恶性肿瘤的检出率也作为观察指标。最终,717(51%)名患者有775处IECFs。其中,109(8%)名患者有115处 潜在临床相关的IECFs;139(10%)名患者有145处可能引起胸痛的 IECFs;469(34%)患者有515处非临床相关的IECFs;19(1.4%)名患者检出未知恶性肿瘤(经组织学证实)。结论心肌灌注PET/CTs患者中,约一半检出IECFs。其中8%的患者,IECFs呈潜在临床相关, 1.4%的患者检查未知恶性肿瘤,且多为肺癌。French AbstractContexteL’objectif de cette étude était d’evaluer la prévalence des anomalies extra-cardiaques (IECF) découvertes sur les images de perfusion myocardique obtenues par tomodensitometrie à positrons, leur signification clinique et le pourcentage de tumeurs non diagnostiquées précédemment.Méthodes et RésultatsDe Septembre 2013 à Février 2016, un total de 1397 patients évalués pour ischemie myocardique par tomodensitometrie à positrons (13NH3) ont été inclus prospectivement dans notre base de données. Les anomalies extra cardiaques découvertes ont été classées en trois groupes: celles ayant une signification clinique importante, celles susceptibles de causer des douleurs thoraciques et celles sans signification clinique. Nous avons également determiné la prévalence de tumeurs thoraciques malignes jusqu’alors inconnues. Chez 717 des patient revus (51%), 775 anomalies extracardiaques ont été signalées. 115 d’entre elles (9%) ont été classées comme potentiellement cliniquement significative (8% des patients). Un total de 145 anomalies susceptibles de causer des douleurs thoraciques a été détecté chez 139 patients (10%). A total de 515 anomalies furent considerées comme cliniquement non significative chez 469 (34%) des patients. Le diagnostic histologique de tumeur primitive (inconnue jusqu’alors) fut etabli chez 19 patients (1.4%).ConclusionsDes anomalies extra-cardiaques peuvent être détectées sur les images de perfusion myocardique par tomodensitometrie à positrons chez environ 50% des patients. Dans la présente étude, les anomalies extra-cardiaques se sont révelées cliniquement significative chez 8% des patients. Parmi ceux-ci, 1.4% furent diagnostiqués avec un cancer (le souvent du poumon).

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

Introduction/AimCorrect staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with 99mTc-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 18F-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.MethodsThe 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.ResultsOne-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.ConclusionOur 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.

Cardiac displacement during 13N-Ammonia myocardial perfusion PET/CT: comparison between adenosine and regadenoson induced stress

This study investigated differences in cardiac displacement during adenosine stress versus regadenoson stress in 13N-ammonia (13NH3) MP PET/CT scans. Methods: In total, 61 myocardial perfusion PET/CT scans were acquired using either adenosine (n = 30) or regadenoson (n = 31) as a stressor. For both groups, cardiac displacement during rest and stress was measured 3-dimensionally, relative to either a fixed reference frame or the previous frame, in each 1-min frame of a list-mode PET acquisition of 25 min. All stress scans were additionally evaluated for the presence of motion artifacts. Also, the tolerability of the agents and the occurrence of side effects were compared between groups. Results: Significantly larger cardiac displacement during stress was detected in the adenosine group than in the regadenoson group, reflected by both maximal cardiac displacement (P = 0.022) and mean cardiac displacement (P = 0.001). The duration of the movement was typically shorter in the regadenoson group. Frames with cardiac displacement of at least 5 mm were observed nearly twice as frequently when adenosine was used instead of regadenoson. Conclusion: The displacement during regadenoson stress is of lower amplitude and shorter duration than that during adenosine stress and may therefore contribute to a lower incidence of motion artifacts on PET/CT scans.

High 18Fluor-DCFPyL Uptake in Adrenal Adenomas

Radioisotope-labeled prostate-specific membrane antigen (PSMA) tracers have been proven accurate for detection of prostate cancer localizations. Uptake of those tracers in other malignant and benign lesions has been reported, including faint accumulation of Ga-PSMA-HBED-CC in adrenal adenoma. A 77-year-old man with prostate carcinoma was scanned with F-DCFPyL, a promising F-labeled PSMA ligand, for prostate-specific antigen progression while on luteinizing hormone-releasing hormone agonist therapy. The PET/CT shows F-DCFPyL uptake in bilateral enlarged adrenals. Non-contrast-enhanced CT scan indicated left adrenal adenoma. Regarding the high positive predictive value of multiphase contrast-enhanced CT (98%), presence of right adrenal adenoma is also likely.

Metastasized 18F-DCFPyL–Negative Prostatic Adenocarcinoma Without Neuroendocrine Differentiation

A 76-year-old man with histopathologically proven prostate cancer (initial prostate-specific antigen 110 ng/mL, Gleason 3 + 4 = 7) received F-DCFPyL PET/CT for initial staging. Both the primary tumor and pathologically enlarged pelvic lymph nodes showed no increased F-DCFPyL uptake. Subsequent histopathologic lymph node biopsy revealed prostate cancer metastasis. Prostate-specific membrane antigen tracers, such as F-DCFPyL, are promising radiopharmaceuticals for prostate cancer imaging. False-negative prostate-specific membrane antigen PET/CT findings have been reported earlier for prostate tumors with neuroendocrine differentiation. However, this report presents false-negative F-DCFPyL PET findings of an adenocarcinoma of the prostate without neuroendocrine differentiation.

Effects of Fasting on 18F-DCFPyL Uptake in Prostate Cancer Lesions and Tissues with Known High Physiologic Uptake

In the literature, a 4- to 6-h fast is recommended before a patient undergoes PET/CT with 2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL); however, a scientific underpinning for this recommendation is lacking. Therefore, we performed a study to determine the impact of fasting on 18F-DCFPyL uptake. Methods: The study included 50 patients who fasted at least 6 h before 18F-DCFPyL administration and 50 patients who did not. Activity (SUVmax) was measured in lesions characteristic of prostate cancer and in normal tissues known to express high physiologic uptake. Results: Uptake in suspected lesions did not differ between the cohorts. 18F-DCFPyL uptake in the submandibular gland, liver, and spleen was significantly higher in the fasting than the nonfasting cohort. Conclusion: Our data show that fasting does not significantly affect 18F-DCFPyL uptake in suspected malignant lesions but does result in significantly lower 18F-DCFPyL uptake in tissues with high physiologic uptake. The absolute differences in uptake were relatively small; therefore, the effects of fasting on the diagnostic performance can be considered negligible.

Biokinetic study of F-18-fluorocholine uptake to differentiate malignant and physiologic uptake of F-18-fluorocholine in prostate cancer metastases

Hypothesis: We assessed in in vitro and in vivo models of ovarian cancer the therapeutic efficacy of 16F12 mAbs directed against Mullerian Inhibiting Substance type II receptor (MISRII) radiolabeled with 213Bi Methods: In vitro, both direct and bystander cytotoxic effects were measured using clonogenic assay and standard medium transfer protocol. Typically, Clonogenic survival was assessed in SK-OV-3 donor cells expressing MISRII and exposed for 90 min to 0.06-0.5MBq/mL of 16F12 213Bi-mAbs. Bystander cytotoxicity was measured in recipient cells grown in non-radioactive culture medium preconditioned for 2 hours in the presence of donor cells. DNA double strand breaks (DSBs) were measured in both donor and recipients cells using immunofluorescent detection of gamma-H2AX and of 53BP1. In vivo we explored in athymic nude mice bearing intraperitoneal (IP) MISRII-expressing AN3CA tumor the therapeutic efficacy of brief-intraperitoneal radioimmunotherapy (BIP-RIT, 12.95 37 MBq; 37MBq/mg) or of intraperitoneal RIT (IP-RIT; 2.96-12.95 MBq; 37MBq/mg) using 213Bi-16F12. BIP-RIT mimics hyperthermic intraperitoneal chemotherapy as used in clinic. It consists of intraperitoneal injection of high activities of radiolabeled mAbs followed 30 min later by wash of the peritoneal cavity with saline solution to remove unbound radioactivity. The biodistribution of radiolabeled antibodies following IP-RIT (12.95 MBq; 37MBq/mg) or BIP-RIT (37 MBq; 37MBq/mg) was assessed. Results: In vitro we showed in donor cells a strong direct cytotoxicity of 16F12 213Bi-mAbs. A significant bystander cytotoxicity was also measured in recipient cells. Genotoxic effects were also demonstrated as measured by the formation of DNA DSBs in both donor and recipient cells. In vivo, results of biodistribution indicated that tumour uptake of 213Bi-16F12 during BIP RIT was higher than after IP RIT. The tumour-to-blood uptake ratio was 9 versus 3, respectively, one hour post RIT while it decreased down to 3 and 1, respectively, three hours post-RIT. Finally, a similar delay in tumor growth was observed in mice treated with 12.95 MBq of 213Bi-16F12 following IP-RIT or treated with 37 MBq using BIP-RIT. Conclusions: We confirmed in vitro the therapeutic efficacy of newly developed 16F12 213Bi-mAbs. in vivo results indicate that similar therapeutic efficacy and lower toxicity could be obtained with BIP-RIT compared with IP-RIT. BIP-RIT could be a new tool in the therapy of peritoneal carcinomatosis. URI: Authors: LADJOHOUNLOU Riad PICHARD Alexandre DEHAYES E BOUDOUSQ Vincent BRUCHERTSEIFER Frank MORGENSTERN Alfred NAVARRO-TEULON Isabelle POUGET Jean-Pierre Publication Year: 2016 Science Areas: Health and consumer protection [1]European Journal of Nuclear Medicine and Molecular Imaging Volume 43, Supplement 1 10.1007/s00259-016-3484-4 This supplement was not sponsored by outside commercial interests. It was funded entirely by the association’s own resources. ABSTRACT DOI 10.1007/s00259-016-3484-4 Eur J Nucl Med Mol Imaging (2016) 43 (Suppl 1):S1–S734Background: In the context of the EORTC LungTech trial, a QA procedure including a PET/CT credentialing has been developed. This procedure will ultimately allow us to pool data from 23 institutions with the overall goal of investigating the impact of tumour motion on quantification. As no standardized procedure exists under respiratory conditions, we investigated the variability of 14 SUV metrics to assess their robustness over respiratory noise. Methods: The customized CIRS-008A phantom was scanned at 13 institutions. This phantom consists of a 18 cm long body, a rod attached to a motion actuator, and a sphere of either 1.5 or 2.5cm diameters. Body, rods and spheres were filled with homogeneous 18FDG solutions representative of activity concentrations in mediastinum, lung and tumour for a 70kg patient. Three respiratory patterns with peak-to-peak amplitudes and periods of 15mm/3sec, 15mm/6sec and 25mm/4sec were tested. Prior to scanning in respiratory condition, a 3D static PET/CT was acquired as reference. During motion, images were acquired using 3D or 4D gated PET(average image) according to institutional settings. 14 SUV(mean) metrics were obtained per acquisition varying VOI/ ROI shape and location. Three ROIs and three VOIs with respective radii of 0.5, 0.6 and 0.8cm were investigated. These ROIs/VOIs were first centred on the maximum activity voxel; a second analysis was made changing the location from the voxel to the region (ROI5voxels) or the volume (VOI7voxels) with the maximum value. Two additional VOIs were defined as 3D isocontours respectively at 70% and 50% of the maximum voxel value. The SUV metrics were normalized by the corresponding 3D static SUV. Converting to recovery coefficients (RC) allowed us to pool data from all institutions, while maintaining focus solely on motion. For each RC from each motion setting we calculated the mean over institutions, we then looked at the standard deviation (Sd) and spread of each averaged RC over each motion setting (formula [1], [2], Figure1). Results: For the institutions visited we found that RCVOI70% and RCVOI50%, yielded over the 14 metrics the lowest variability to motion with Sd of 0.04 and 0.03 respectively. The RCs based on ROIs/VOIs centered on a single voxel were less impacted by motion (Sd: 0.08) compared to region RCs (Sd: 0.14). The averaged Sd over the RCs based on VOIs and ROIs was 0.12 and 0.11 respectively. Conclusion: Quantification over breathing types depends on ROI/VOI definition. Variables based on SUV max thresholds were found the most robust against respiratory noise.