[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

[18F]-JK-PSMA-7 and [18F]-FDG tumour PET uptake in treated xenograft human prostate cancer model in mice.

PURPOSE: This preclinical study aims to evaluate the extent to which a change in prostate-specific membrane antigen (PSMA) expression of castration-resistant prostate cancer (CRPC) following standard treatment is reflected in [18F]JK-PSMA-7 PET/CT. METHODS: Castrated mice supplemented with testosterone implant were xenografted with human LNCaP CRPC. After appropriate tumour growth, androgen deprivation therapy (ADT) was carried out by the removal of the implant followed by a single injection of docetaxel (400 µg/20-g mouse) 2 weeks later. [18F]JK-PSMA-7 PET/CT were performed before ADT, then before and at days 12, 26, 47 and 69 after docetaxel administration. The [18F]JK-PSMA-7 PET data were compared to corresponding unspecific metabolic [18F]FDG PET/CT and ex vivo quantification of PSMA expression estimated by flow cytometry on repeated tumour biopsies. RESULTS: ADT alone had no early effect on LNCaP tumours that pursued their progression. Until day 12 post-docetaxel, the [18F]JK-PSMA7 uptake was significantly higher than that of [18F]FDG, indicating the persistence of PSMA expression at those time points. From day 26 onwards when the tumours were rapidly expanding, both [18F]JK-PSMA7 and [18F]FDG uptake continuously decreased although the decrease in [18F]JK-PSMA uptake was markedly faster. The fraction of PSMA-positive cells in tumour biopsies decreased similarly over time to reach a non-specific level after the same time period. CONCLUSION: Applying PSMA-based imaging for therapy monitoring in patients with CRPC should be considered with caution since a reduction in [18F]JK-PSMA-7 PET uptake after successive ADT and chemotherapy may be related to downregulation of PSMA expression in dedifferentiated and rapidly proliferating tumour cells.

Clinico-metabolic characterization improves the prognostic value of histological growth patterns in patients undergoing surgery for colorectal liver metastases.

BACKGROUND AND OBJECTIVES: The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value. METHODS: In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with 18 Fluorodeoxyglucose/positron emission tomography. RESULTS: In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients. CONCLUSIONS: Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.

Monitoring metabolic response using FDG PET-CT during targeted therapy for metastatic colorectal cancer.

INTRODUCTION: The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient's unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine. METHODS: This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding. RESULTS: On baseline FDG PET-CT, 124 measurable "target" lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis. CONCLUSIONS: Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.

18F-JK-PSMA-7 PET/CT for staging intermediate- or high-risk prostate cancer patients before radical prostatectomy: a pilot study.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) using radiotracers that bind to the prostate-specific membrane antigen (PSMA) is mainly used in biochemical recurring prostate cancer. The aim of our study was to assess the usefulness of 18F-JK-PSMA-7 PET/CT for local and nodal staging in patients with intermediate- and high-risk prostate cancer (PCa) prior to radical prostatectomy, as compared to conventional imaging techniques. METHODS: We enrolled a total of 10 patients with intermediate- and high-risk PCa diagnosed by multiparametric-MRI followed by systematic and targeted biopsies, eligible for radical prostatectomy with extended lymph node dissection. Clinical team was blind to the results of the pre-surgery 18F-JK-PSMA-7 PET/CT at times of clinical decision and surgery. One month post-surgery, 18F-JK-PSMA-7 PET/CT was repeated and the results of both scans were unblinded. A third 18F-JK-PSMA-7 PET/CT could be acquired at a later time point depending on PSA progression. RESULTS: All pre-surgery 18F-JK-PSMA-7 PET/CT was positive in the prostatic region, while MRI was negative in the prostate in one patient. We also detected positive pelvic lymph nodes in two patients (one high-risk, one intermediate-risk PCa) on pre-surgery and post-surgery 18F-JK-PSMA-7 PET/CT. No positive pelvic lymph nodes were reported on pre-surgical CT and MRI. 18F-JK-PSMA-7 PET/CT detected bladder involvement in one patient and seminal vesicles involvement in two patients; this malignant extension was undetected by the conventional imaging techniques. SUVmax in prostate lesions had an average value of 11.51 (range 6.90-21.49). SUVmean in prostate lesions had an average value of 7.59 (range 5.26-14.02). CONCLUSION: This pilot study indicates that pre-surgery 18F-JK-PSMA-7 PET/CT provides valuable information in intermediate- and high-risk PCa, for surgery planning with curative intent.

Recurrent 'Occult' 18F-FDG Uptake in an Atypical Case of Anti-Myeloperoxidase Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

A 72-year-old woman, with anti-myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presented with two episodes of spinal pachymeningitis (at two different levels 9 years apart, cervical in 2011 and dorso-lumbar in 2020) associated with aortitis and only demonstrated by F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). This association between aortitis and pachymeningitis in AAV appears exceptional. Moreover, the relapse of aortitis and pachymeningitis in 2020 was not accompanied by an increase in ANCA. This case demonstrates the value of 18F-FDG PET/CT in the management of AAV, providing evidence of the recurrence and distribution of lesions in various organs, including those with unexpected involvement. LEARNING POINTS: Involvement of large vessels such as the aorta is rarely associated with anti-myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but has been described in a few cases. Possible aortic involvement should always be kept in mind while managing a patient with AAV.Pachymeningitis is rarely associated with AAV, but in case of unexplained and unspecific neurological symptoms in patients with AAV, such involvement should be considered.18F-FDG PET/CT is a promising tool for the management of patients with AAV, allowing unexpected sites, undetected by usual examinations, to be highlighted. In contrast to giant-cell arteritis, this exam has not, until now, been included in the recommended/systematic work-up of AAV.

Bilateral cytomegalovirus infection of the adrenal glands revealed by 18F-FDG PET/CT in a patient with T-cell lymphoma.

This case report demonstrates the possible subclinical adrenal and pancreatic involvement in immunocompromised patients (in particular those with lymphoma) with a CMV infection and the role of whole-body 18F-FDG PET/CT in detecting these lesions.

Comparison of PMT-based TF64 and SiPM-based Vereos PET/CT systems for 90 Y imaging and dosimetry optimization: A quantitative study.

BACKGROUND: Selective internal radiotherapy based on transarterial radioembolization (TARE) with yttrium-90 (90 Y) microspheres is an established treatment for primary or metastatic liver disease. PURPOSE: The objective of this work is to optimize the dosimetry of patients treated with 90 Y TARE, using positron emission tomography (PET) images. METHODS: The NEMA 2012 PET phantom was filled with nearly 3.9 GBq of 90 Y activity and acquired at days 0, 3, 5, 7, and 9 on a classic time-of-flight PET/computed tomography (CT) scanner (Philips TF64) and on a silicon photomultiplier (SiPM)-based PET/CT scanner (Philips Vereos). Acquisitions were carried on following the guidelines proposed in a previously published multicentric trial and images were reconstructed by varying and combining the available parameters. Comparisons were performed to identify the best set(s) of parameters leading to the most accurate 90 Y-PET image(s), in terms of activity distribution. Then, for both scanners, the best images were analyzed with Simplicit90 Y, a personalized dosimetry software using multicompartmental Medical Internal Radiation Dose model. The comparison between measured and true doses allowed to identify the image granting the most consistent dose estimations and, therefore, to designate the set of parameters to be applied on patients' data for the reconstruction of optimized clinical images. Posttreatment dosimetry of four patients was then realized with Simplicit90 Y using optimized imaging datasets. RESULTS: Based on activity distribution comparisons and dose estimations over phantom and patients data, the SiPM-based PET/CT system appeared more suitable than the photomultiplier tube-based TF64 for 90 Y-PET imaging. With the SiPM-based PET/CT system, reconstructed images with a 2-mm voxel size combined with the application of the point spread function correction led to the most accurate results for quantitative 90 Y measures. CONCLUSIONS: For the SiPM-based PET/CT scanner, an optimized set of reconstruction parameters has been identified and applied on patients' data in order to generate the most accurate image to be used for an improved personalized 90 Y-PET dosimetry, ensuring a reliable evaluation of the delivered doses.

Clinical experience with 18F-JK-PSMA-7 when using a digital PET/CT.

BACKGROUND: Digital PET/CT systems make use of a new technology with higher sensitivity and other better technological features than the analog ones. They require adaptation of the trade-off between performance, tracer dose and acquisition time. The aim of the study was to explore the performance of 18F-JK-PSMA-7 imaging when performed on a digital PET/CT with an adapted protocol, in a population of patients with prostate cancer patients (PCa). Influence of previous therapy on PET/CT performance is generally disregarded in PSMA-based imaging, despite potential influence of hormono-chemotherapy on the target expression. This potential influence was also tested in this work. METHODS: A total of 54 PCa patients experiencing biochemical recurrence were included in the study, in which we analysed the diagnostic performance of digital 18F-JK-PSMA-7 PET/CT. Compared to our protocol applied for acquisition on an analog system, administered dose and acquisition time were reduced by 20% and 50% respectively. We specifically took into consideration the influence of previous treatments on recurrence detection. RESULTS: We detected overall 18F-JK-PSMA-7-positive lesions in 38/54 patients (70.3%). There was no statistically significant difference regarding the detection rate between the groups of patients who had hormono-chemotherapy any time after initial diagnosis and those who never got any hormonal or chemotherapeutic treatment. Regarding the SUV max values, there was not significant difference between the two groups of patients neither in pelvic ganglions nor in other metastatic sites or the prostate region. CONCLUSION: 18F-JK-PSMA7 PET/CT with administered dose and acquisition time adapted to the digital technology provides valuable information in PCa patients with biochemical recurrence.

Rapid Progression of Angioimmunoblastic T Cell Lymphoma Following BNT162b2 mRNA Vaccine Booster Shot: A Case Report.

Since nucleoside-modified mRNA vaccines strongly activate T follicular helper cells, it is important to explore the possible impact of approved SARS-CoV-2 mRNA vaccines on neoplasms affecting this cell type. Herein, we report and discuss unexpected rapid progression of lymphomatous lesions after administration of a BNT162b2 mRNA vaccine booster in a man recently diagnosed with AITL.

Prospective Serial FDG PET/CT During Treatment of Extrapulmonary Tuberculosis in HIV-Infected Patients: An Exploratory Study.

PURPOSE: The aim of this study was to prospectively describe evolution of F-FDG uptake of extrapulmonary tuberculosis (TB) throughout the course of TB treatment in HIV patients to evaluate F-FDG PET/CT as a monitoring tool of treatment response. METHODS: We performed baseline FDG PET/CT, PET-2 after 2 months, and PET-3 at the end of TB treatment in 18 HIV/TB patients. We correlated evolution of FDG uptake with clinical outcome of patients. RESULTS: After 2 months of treatment, 78% of the patients had a significant metabolic response. Lymph node (LN) metabolic response was heterogeneous, with 57% of LN sites showing decreased SUVmax and 41% showing unchanged FDG uptake. Organs other than LNs showed more homogeneous response. The FDG PET/CT performed at the end of TB treatment showed a complete response of all infected organs and a drastic response in terms of active LNs in 95% of the patients (SUVmax mean decrease = 85%, median = 100%). A complete metabolic response after TB treatment was seen in only 47% of patients. CONCLUSIONS: In difficult-to-treat entities such as extrapulmonary TB in HIV patients, FDG PET/CT is a potential tool in monitoring TB treatment response and should be explored in larger studies.

MR imaging versus PET/CT for evaluation of pancreatic lesions.

PURPOSE: To retrospectively determine the diagnostic accuracy of magnetic resonance imaging (MRI) and combined positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of benign and malignant pancreatic lesions. MATERIALS AND METHODS: Twenty-seven patients (15 women/12 men, mean age 56.5 years) with MR imaging and PET/CT studies performed to differentiate benign and malignant pancreatic lesions were identified between October 2008 and October 2010. Both MR and PET/CT data sets were retrospectively and blindly evaluated by two independent readers (4 readers total) with different degrees of experience, using a visual five-point score system. The results were correlated with final diagnosis obtained by histopathology. RESULTS: 17 patients had malignant diseases and 10 patients had benign diseases. Depending on the observer, the sensitivity, specificity, positive predictive value and negative predictive value of MRI varied between 88-94%, 50-80%, 75-89% and 71-89% respectively. Sensitivities, specificities, positive predictive values and negative predictive values of PET/CT were 73%, 56%, 73% and 56% respectively. The diagnostic accuracy of MR for the differential diagnosis of pancreatic lesions was 74-89%, compared with 67% for PET/CT. The weighted Cohen's kappa coefficient was 0.47 at MR and 0.53 at PET/CT. CONCLUSION: MRI achieved higher sensitivity and specificity in the differential diagnosis of pancreatic lesions.