Prognostic value of functional tumor burden on 68Ga-DOTATOC PET/CT in patients with pancreatic neuro-endocrine tumors.

Despite their relative quiescence, pancreatic neuro-endocrine tumors (pNET) can correspond to various presentations and outcomes. Several prognostic factors have been identified, including maximal standardized uptake value of the most intense focus (maxSUVmax) on Positron Emission Tomography (PET) with a somatostatin analogue. Herein, we investigate the prognostic value on progression free-survival of the total functional tumor volume (TFTV) measured by 68Ga-DOTATOC PET. From patients who underwent 68Ga-DOTATOC PET from 2008 to 2014, we selected consecutive patients with G1 or G2 pNET (2010 World Health Organization classification), at least one abnormal focus on PET and available follow-up data. TFTV was computed by summing the volumes of all pathological foci, delineated use of 41% of its SUVmax for each threshold focus. Fifty patients were included. During the follow-up period, 33 patients had stable or responsive disease (66%; median duration 28.5 months; range 6.3-77.7 months) and 17 patients experienced disease progression (34%; median progression time 21 months; range 6.7-44.7 months). Median PFS was 43.5 months. The best TFTV cut-off for predicting progression within 24 months was 13.8 cm3. Multivariate analysis determined that TFTV greater than 13.8 cm3 was the only criterion considered a significant risk factor for tumor progression (HR 2.9; p=0.0003). A significant difference in PFS was observed for TFTV (<13.8 vs. ≥ 13.8 cm3: median not reached vs. 25 months; p=0.0001). Our study suggests that 68Ga-DOTATOC TFTV measured on PET images is a valuable prognostic biomarker in patients with well-differentiated pNETs of all stages.

[PET/CT and biochemical recurrence of prostate adenocarcinoma: Added value of 68Ga-PSMA-11 when 18F-fluorocholine is non-contributive]. / TEP/TDM et récidive biologique d'adénocarcinome prostatique : apport du 68Ga-PSMA-11 lorsque la 18F-fluorocholine n'est pas contributive.

INTRODUCTION: Since April 201, we have introduced PET/CT using a ligand of prostate-specific membrane antigen labeled with gallium-68 (PSMA-11). We aimed to evaluate its positivity rate and impact in patients presenting biochemical recurrence of prostate cancer whose 18F-fluorocholine (FCH) PET/CT was non-contributive. PATIENTS AND METHOD: Patients were prospectively included between April and December 2016. PET/CT was performed 60min after injection of 2MBq/kg of body mass of 68Ga-PSMA-11. Three anatomical areas were considered: prostatic lodge, pelvic lymph nodes and distant locations. The impact of PSMA-11 PET/CT was assessed by comparing changes in therapeutic strategy decided during multidisciplinary meeting. RESULTS: Thirty-three patients were included. The mean PSA serum level measured on the month of the PSMA-11 PET/CT was 2,8ng/mL. Twenty-five (76%) PSMA-11 PET/CT were positive, 7 (21%) negative and 1 (3%) equivocal. Of 11 patients whose FCH PET/CT showed equivocal foci, PSMA-11 PET/CT confirmed those foci in 5 cases. Follow-up was available for 18 patients (55%). PSMA-11 PET/CT results led to a change in management in 12 patients (67%). CONCLUSION: 68Ga-PSMA-11 PET/CT is useful in detecting recurrence of prostate cancer, by identifying residual disease which was not detected on other imaging modalities and by changing management of 2 patients out of 3. LEVEL OF EVIDENCE: 5.

Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone.

Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-[¹8F]fluoro-17ß-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV(max) or FES/FDG SUV(max) ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical utility in those settings; only initial results are available. The indication of PET and PET/CT has been even more disputed in prostate carcinoma, due to the lack of significant FDG uptake in most cases, at least before the castration-resistant stage. Using FDHT, a fluorinated testosterone analogue, PET is able to detect the over-expression of the androgen receptor (AR) in lesions, at a whole-body level. At least partly due to the rather large number of alternative tracers that are in development or even routinely available in some countries, few FDHT studies have been published until now. From absorbed dose values previously published for FES by the team of University of Washington School of Medicine at Seattle, and for FDHT by the teams of Memorial Sloan-Kettering Cancer Center at New York and of Washington University at St. Louis, we applied the coefficients of ICRP publication 103 and calculated an effective dose per unit of injected activity of 0.023 mSv/MBq for FES and 0.018 mSv/MBq for FDHT. The radiation exposure is of the same order of magnitude as with FDG.

What is currently the best radiopharmaceutical for the hybrid PET/CT detection of recurrent medullary thyroid carcinoma?

Among thyroid malignancies, medullary thyroid carcinoma (MTC) has some very specific features. Production and secretion of large amounts of peptides occur in malignant transformed C cells with few exceptions, leading to high serum levels of calcitonin (Ctn) and carcinoembryonic antigen (CEA), that act after thyroidectomy as tumour markers warning for the presence of persistent or metastatic MTC. The availability of those serum biomarkers with an excellent sensitivity challenges medical imaging to localise the recurrent cancer tissue, since surgery is a major therapeutic option. The aims of this article are (i) to review literature evidence about the efficacy and tolerance of radiopharmaceuticals for 3 targets of PET/CT imaging (glucose metabolism, bioamines metabolism and somatostatin receptors) and also bone scintigraphy which is recommended in the Guidelines of European Society for Medical Oncology (ESMO; (ii) to compare the availability and the costs in relation with those radiopharmaceuticals, (iii) and to discuss a possible sequence of those examinations, in order to optimise spending and to minimise the overall radiation dose. In this context of recurrent MTC suspected on rising tumour markers levels after thyroidectomy, this survey of literature confirms that FDOPA is the best radiopharmaceutical for PET/CT with significant diagnostic performance if Ctn>150 pg/mL; an early image acquisition starting during the first 15 min is advised. In negative cases, FDG should be the next PET radiopharmaceutical, in particular if Ctn and CEA levels are rapidly rising, and PET with a somatostatin analogue labelled with gallium-68 when neither FDOPA nor FDG PET are conclusive. Bone scintigraphy could complement FDG-PET/CT if FDOPA is not available.

Metabolic syndrome and its effect on aortic stiffness in premenopausal women.

BACKGROUND: Metabolic syndrome (MS) is a cluster of proatherogenic risk factors (RF) (abdominal obesity, atherogenic dyslipidemia, impaired fasting glucose or type 2 diabetes mellitus, higher blood pressure or antihypertensive therapy) that move patients into a higher risk for development of cardiovascular disease (CVD) and type 2 diabetes. The preclinical (subclinical) target organ diseases (SOD) are early signs of atherosclerosis. An increased aortic stiffness characterised by an increased pulse wave velocity in aorta (PWV Ao) is one of SOD.The aim of the present study was to assess the impact of metabolic syndrome (MS) on aortic wall stiffness and the risk profile in premenopausal women. METHODS: The aortic stiffness was measured using Arteriograph-Tensiomed, based on oscillometric measurement and analysis of the shape of brachial pulse wave, giving the PWV Ao. The results of measurements characterise a global aortic stiffness. RESULTS: We examined 81 premenopausal women (without history of CVD). The MS (according to the 2009 "harmonizing" definition) was present in 31 women (mean age 41.5 y), in the control group, there were 50 women (39 y). The most frequent components of MS were abdominal obesity (93 % vs 42%), arterial hypertension (68 % vs 10 %) and dyslipidemia (29 % vs 8 %). The PWV Ao was significantly higher in women with MS (9.26 m/s) compared to the control group (7.44 m/s). CONCLUSION: The aortic stiffness in women with MS compared to controls was significantly higher despite a presumed general protective hormonal effect on cardiovascular system in women with child-bearing potential (Tab. 4, Ref. 25).

Diagnosis of bone metastasis: recent comparative studies of imaging modalities.

Various imaging modalities are currently available to diagnose bone metastasis. The two main anatomical modalities are computed tomography (CT) and magnetic resonance imaging (MRI), with many variants proposed for the MRI procedure, including diffusion-weighted imaging. The two main functional modalities are scintigraphy and PET, also with many variants in the radiopharmaceutical, from the "all purpose" 99mTc labelled bisphosphonates to very selective radiopharmaceuticals for rare neoplasia. The diagnostic strategy will become more and more individually tailored according to the patient's clinical and biological data (primary cancer type, phase of the evolution, markers of aggressiveness, serum levels of biological tracers of bone metabolism, circulating or disseminating tumour cells …). If imaging is indicated, the diagnostic strategy will also depend on the availability and the diagnostic performance of the imaging modalities. Assessment of diagnostic performance requires comparative studies, performed with an adequate methodology. The main methodological weaknesses encountered in studies intending to compare imaging modalities for diagnosing bone metastasis are summarised. Comparative studies have been reviewed, which address the initial diagnosis of skeletal metastases in solid tumours except primary bone cancers. The results of more than 140 such comparative studies are then summarised and briefly commented, according to the type of the primary cancer, and according to the compared imaging modalities.

Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate cancer: prospective comparison of diagnostic performance determined by masked reading.

AIM: The aim of this paper was to compare the diagnostic performance of positron emission tomography/computed tomography (PET/CT) with fluorocholine (18F) (FCH) or fluoride(18F) (FNa) for the detection of bone metastasis in patients with prostate cancer complaining from osteoarticular pain, taking into account whether they were referred for initial staging or recurrence localization. The initial hypothesis was that FCH site-based specificity would be superior to that of F Na, with no loss in sensitivity. METHODS: Forty-two patients were enrolled in this prospective study, underwent both PET/CTs and were then followed-up for at least 6 months. The standard of truth (SOT) about the presence/absence and location of bone metastasis could be determined in 40 patients, by 2 independent medical assessors, blinded to the results of both PET/CTs. The comparison was performed according to the guideline of the European Medicines Agency, i.e. based on the results of blind reading with SOT as reference. RESULTS: Bone extension was present in 22 patients and absent in 18. Patient-based performance for FCH vs. FNa was 91% vs. 91% for sensitivity, 89% vs. 83% for specificity and 90% vs. 88% for accuracy (no significant difference). Of 360 skeletal sites, 68 were malignant and 292 non-invaded. There was no significant difference in site-based performance in the group of patients referred at initial staging, but in the group of patients referred for suspicion of recurrence, FCH was significantly more specific than FNa (96% vs. 91%, P=0.033 with Obuchowski's correction) while sensitivity was the same, 89%. CONCLUSION: Both radiopharmaceuticals, based on a very different metabolic approach, showed good diagnostic performance. If FCH is available, it should be preferred in patients after initial treatment.

From preoperative to intraoperative detection of hyperfunctioning parathyroid glands using tetrofosmin (99mTc) in primary hyperparathyroidism.

The impact of preoperative scintigraphy on the management of patients with primary hyperparathyroidism has been largely documented for more than two decades. More recently, preoperative scintigraphy has also been used to select patients for intraoperative detection of hyperfunctioning parathyroid glands thanks to a gamma-probe. This procedure is now widely used, with MIBI as the main radiopharmaceutical for both preoperative scintigraphy and intraoperative detection. However MIBI was not available in Slovakia until very recently and tetrofosmin (TF), the alternative 99mTc labelled radiopharmaceutical for myocardial imaging has some advantages over MIBI and a close biological behaviour. Thus we have been using TF also for parathyroid preoperative scintigraphy and for intraoperative detection, a systematic indication which has never been reported by others. This article aims to demonstrate the feasibility and to present our protocol for TF parathyroid imaging and intraoperative detection, closely associating surgeons, nuclear medicine specialists, pathologists and also biologists as intraoperative assay of intact PTH is necessary. The results of literature are subsequently reported and discussed (Tab. 2, Fig. 4, Ref. 35). Full Text in free PDF www.bmj.sk.

[Fluoroethylthyrosine 18F PET in the detection of brain tumours]. / TEP à la fluoroéthyltyrosine (18F) pour la détection des tumeurs cérébrales.

UNLABELLED: PET with fluoroethylthyrosine (FET), amino-acid analogue, has been performed in Germany since the beginning of the decade for molecular and metabolic imaging of brain tumours, since FDG, the glucose analogue which is the reference tracer for clinical PET, has this drawback to be taken-up intensely by cerebral cortex. We report on our preliminary results on the comparison of PET/CT with FET and FDG in 10 evaluable patients presenting with a brain lesion either at diagnosis or after treatment. In an attempt to optimise specificity, FET PET/CT has been acquired as a static image 1h after injection, while the most current practice is a dynamic 40 min acquisition starting at FET injection. With our acquisition protocol, diagnostic performance of FET was 88% sensitivity and 80% accuracy vs 13% and 30% respectively for FDG. CONCLUSION: FET is a radiopharmaceutical with clinical usefulness for the diagnosis, delineation and monitoring of brain tumours. Association with FDG allows identification of high-grade lesions or components, but it could be avoided providing that acquisition and quantification procedures of FET PET/CT would have been better optimised and standardised.

Prospective comparison of FDG and FET PET/CT in patients with head and neck squamous cell carcinoma.

AIM: The clinical usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) in head and neck squamous cell carcinoma (HNSCC) is now well-documented. However, its sensitivity is greater than its specificity due to false-positive results in inflammatory or infectious lesions, which are frequent in this area, in particular after treatment by surgery and/or radiotherapy. O-2-fluoro-(18F)-ethyl-L-thyrosine (FET) has been reported not to be taken up by such lesions, and a preliminary study indicated that this may be clinically useful in HNSCC. We performed a prospective study to compare the diagnostic performances of FDG and FET PET/CT in the different settings of HNSCC. MATERIALS AND METHODS: Twenty-seven patients (20 men and seven women, aged 48-76, among 30 patients included) and 69 suspected cancer sites are now evaluable on basis of postsurgical histology and/or follow-up greater than 6 months; 15 patients were referred for initial staging and 12 during posttherapy follow-up, a recurrence being suspected in eight of them. FDG and FET PET/CT were performed on two different days, the patient fasting for 6 h, 1 h after injection of 5 MBq/kg of body mass of each radiopharmaceutical. Both PET/CT examinations were blind read more than 6 months after the end of inclusions in a random order for each tracer and with a time interval greater than 1 month between FDG and FET PET/CT blind readings. RESULTS: Overall diagnostic performances, derived from blind reading: FDG PET/CT on a per patient basis: sensitivity 100%, specificity 71%, accuracy 93%; FDG PET/CT on a per site basis: sensitivity 95%, specificity 63%, accuracy 83%; FET PET/CT on a per patient basis: sensitivity 70%, specificity 100%, accuracy 78%; FET PET/CT on a per site basis: sensitivity 64%, specificity 100%, accuracy 78%. At site level, sensitivity was significantly greater with FDG (p<0.02) and specificity with FET (p<0.01). The statistical level of significance was not reached at patient level. CONCLUSION: Although its good specificity was confirmed, FET did not appear to be suited as a first-line PET tracer in HNSCC imaging and cannot replace FDG for staging due to insufficient sensitivity. However, it was useful in a few selected cases to favor a wait and see attitude when a FDG+ FET- focus was discovered in patients referred for systematic FDG PET during follow-up. In contrast, second primary cancers should not be ruled out if FDG was clearly positive in the lungs or the digestive tract.

[[18F]-FDG imaging in apparently isolated pleural lesions]. / L'imagerie nucléaire au [18F]-FDG dans les lésions pleurales en apparence isolées.

UNLABELLED: While a great deal of work has been performed concerning the impact of [18F]-FDG imaging in isolated lung lesion(s), there are still very few data about its role in case of isolated pleural lesions. The aim of this preliminary study was to shed some light on the utility of [18F]-FDG imaging, using PET or CDET detection, in this context. PATIENTS AND METHOD: Sixteen patients referred for apparently isolated pleural lesions were included in this study, since their 22 [18F]-FDG examinations were evaluable on bases of histology (9 cases), rapid disease progression (4 cases) or a follow-up period of more than 6 months (9 cases). Twelve [18F]-FDG examinations were performed with a dedicated PET machine (C-PET, Adac) and ten with a coincidence detection gamma camera (Irix, Picker). The precise clinical settings were the following: characterization of pleural masses or search for the unknown primary tumor in case of adenocarcinoma (6 cases), staging of a mesothelioma (5 cases), suspicion of recurrence and/or residual lesions (11 cases). RESULTS: The malignant pleural lesions took up [18F]-FDG in all cases. There was one false positive result due to an inflammatory lesion. False negative results for the detection of lymph node invasion occurred in three patients and were in relation with their infracentimetric size and the difficulty to distinguish on [18F]-FDG images mediastinal lymph nodes from widespread pleural and pulmonary extension of cancer. A change in patient management resulted from the [18F]-FDG examination in 4 patients (25%) and the course confirmed that the change was correct. Unknown lesions or active lesions wrongly considered residual that could have modified the management were discovered in 3 other patients. CONCLUSIONS: This study highlights the fact that [18F]-FDG imaging has an impact on the management of patients with solitary pleural lesions and can detect recurrences, in some cases even more accurately than invasive procedures with histology. In our limited experience, the lack of anatomical details of the PET images is a major drawback in this setting and we are convinced that PET-CT will substantially enhance the impact of [18F]-FDG imaging.