Hyperparathyroidism in pregnancy and 99mTc-MIBI scintigraphy.

INTRODUCTION: Primary hyperparathyroidism (PHPT) during pregnancy can be responsible for serious maternal and foetal complications and should be treated by elective low-risk, minimally invasive surgery. Preoperative assessment of hyperfunctioning parathyroid glands is classically based on high-resolution neck ultrasound (US) and 99mTc-sestamibi/123I scintigraphy. However, administration of any radiopharmaceutical during pregnancy must be limited and justified and US alone may be sufficient to localize an abnormal parathyroid gland. CASE REPORT: We report the case of a 4-month pregnant woman with severe primary hyperparathyroidism, in whom US failed to localize the abnormal parathyroid gland. 99mTc-sestamibi scintigraphy was performed in preference to 18-fluorocholine (FCH)-PET/CT on the basis of a multidisciplinary decision. As 99mTc-MIBI demonstrated an hyperfunctioning right inferior parathyroid, 123I was not administered. A large right paravertebral parathyroid adenoma was successfully removed, as confirmed by decreased postoperative serum parathyroid hormone and calcium levels. The eutrophic newborn infant was delivered at term, with normal serum calcium and TSH levels. DISCUSSION: In pregnant women with primary hyperparathyroidism, US alone may be sufficient when it localizes the abnormal parathyroid gland, allowing elective low-risk minimally invasive surgery. Otherwise, a multidisciplinary approach is mandatory to select the radiopharmaceutical that can be safely used to identify the hyperfunctioning parathyroid gland with minimal risks for the foetus.

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.

Best sensitivity of 18F-FDOPA PET/CT to detect metastasis in one case of neuroendocrine tumour of the ileum. / Mejor rendimiento de la PET/TC con 18F-FDOPA para la detección de metástasis de un tumor neuroendocrino del íleon.

Neuroendocrine tumours (NET) are heterogeneous and frequently spread over the body, making their imaging difficult. With this aim, nuclear medicine imaging, using PET or SPECT with different tracers, has been proposed for decades, but there is currently no consensus on the most appropriate technique, even when only considering gastrointestinal NET. The case is presented of a 67year old woman with a well differentiated NET of the ileum with suspected recurrence, which was not detected by any imaging technique except 18F-FDOPA PET/CT. Subsequent follow up showed disease progression, which confirmed the true positivity of 18F-FDOPA. Using this case, we discuss and compare different radiotracers for the diagnosis of gastrointestinal NET, focusing on those embryologically originating from the mid-gut.

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.

(68)Ga-AMBA and (18)F-FDG for preclinical PET imaging of breast cancer: effect of tamoxifen treatment on tracer uptake by tumor.

INTRODUCTION: AMBA is a bombesin analogue that binds to GRPr. In a mouse model of estrogen-dependent human breast cancer, we tested whether (68)Ga-AMBA can be used for PET detection of GRPr-expressing tumors and could be more accurate than (18)F-FDG to monitor tumor response to hormone therapy. METHODS: The radiolabeling of (68)Ga-AMBA was automated using a R&D Synchrom module. ZR75-1, a breast cancer cell line, was xenografted in nude mice. (68)Ga-AMBA tumor uptake was compared with that of (18)F-FDG before and after treatment with tamoxifen. RESULTS: AMBA was (68)Ga-radiolabelled in 30min with 95.3% yield and purity≥98%. Prior to treatment, (68)Ga-AMBA was highly concentrated into tumors (tumor to non-tumor ratio=2.4 vs. 1.3 with (18)F-FDG). With tamoxifen treatment (n=6) (68)Ga-AMBA uptake plateaued after 1week and decreased after 2weeks, with a significant reduction compared to controls (n=4). In contrast the effect of tamoxifen treatment could not be appreciated using (18)F-FDG. CONCLUSIONS: (68)Ga-AMBA appeared better than (18)F-FDG to visualize and monitor the response to hormone treatment in this breast cancer model.

Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group.

Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique.

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.

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.

[Impact of positron emission tomography on clinical management of potentially resectable non-small-cell lung cancer: a French prospective multicenter study]. / Impact de la tomographie par émission de positons au 18-FDG dans la prise en charge des patients porteurs d'un cancer bronchique non à petites cellules a priori opérable. Etude prospective multicentrique française.

BACKGROUND: Whole-body (18)F-deoxyglucose positron emission tomography (FDG-PET) has the potential to improve the management of non-small-cell lung cancer (NSCLC). We prospectively evaluated the impact of combining FDG-PET with conventional staging methods, including computed tomography (CT), on the staging and management of patients with potentially resectable NSCLC. METHODS: Ninety-four consecutive patients with newly diagnosed/suspected NSCLC were enrolled. Each patient was first staged by using conventional methods, and then by FDG-PET. FDG-PET results were forwarded in a sealed envelope and divulged at the weekly staff meeting on staging and treatment, only after "Decision 1", based on conventional staging, had been reached by consensus; reevaluation taking FDG-PET into account yielded "Decision 2". The validity of these latter decisions was analyzed retrospectively. RESULTS: Eighty-nine patients were eligible. Relative to standard imaging, FDG-PET led to clinical staging changes in 26 (29.2%) patients. The stage was lowered in eight cases (9%) and raised in 18 cases (20.2%). "Decision 2" differed from "Decision 1" in 19 patients, modifying the surgical procedure in four cases, indicating other investigations to confirm FDG-PET evidence of metastases in 12 cases, or modifying the medical treatment in three cases. These modifications were retrospectively justified in 9/19 cases, and consisted of 2/4 modifications of the surgical procedure (one hilar and one adrenal metastasis not confirmed histologically), 4/12 further investigations (axillary and liver biopsies, mediastinoscopy, occult colon cancer) and three indications for palliative treatment, in patients who all died within 3 months after FDG-PET. CONCLUSIONS: Based on FDG-PET, management was modified in 19/89 (21.3%) patients, but these changes were justified in only 9/89 patients (10.1%). FDG-PET can detect asymptomatic local and distant metastases and improves the preoperative assessment of NSCLC, thereby avoiding unnecessary surgery. However, histological verification is required because of the risk of false-positive results.

[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.

[Use of PET for staging, treatment evaluation, and follow-up in esophageal cancers]. / Apport de la TEP au diagnostic, évaluation thérapeutique et suivi du cancer de l'oesophage.

FDG-(18F) PET can now be usually included in the treatment strategy of esophageal cancers for the pretreatment staging in operable tumours or for the diagnosis of recurrence. PET is also a good tool in conformal radiation therapy for improving the target coverage to treat the metabolic target volume or the biological target volume. Furthermore, PET seems to be interesting for evaluation of tumour response and could modify the treatment strategy after neoadjuvant chemotherapy or concurrent chemotherapy and radiation therapy. New radiotracers could allow advances in biological and molecular tumour delineation and contribute to change in treatment strategy based on functional and biological imaging.

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.

MRI and FDG PET/CT findings in a case of probable Heidenhain variant Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disease caused by the accumulation of a pathogenic isoform of a prion protein in neurons that is responsible for subacute dementia. The Heidenhain variant is an atypical form of CJD in which visual signs are predominant. This is a report of the case of a 65-year-old man with probable CJD of the Heidenhain variant, with topographical concordance between findings on magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) photopenic areas on positron emission tomography (PET)/computed tomography (CT) for cortical parietooccipital lesions.

[Imaging and PET-CT of adult and childhood lymphoma]. / Imagerie radiologique et TEP scanner des lymphomes de l'adulte et de l'enfant.

Malignant lymphomas are lymphoproliferative disorders arising in both lymphoid tissue and non-lymphoid organ systems. Treatment rarely is surgical, and currently relies on a combination of chemotherapy and radiation therapy. The role of imaging is to determine the spread of the disease, to identify targets and to assess therapeutic response. Imaging techniques mainly use morphological criteria, and may underestimate infiltrative disease, as observed in bones. The frequent presence of residual masses after treatment usually prevents classification of patients as complete response. Over time, positron emission tomography (PET) with F18-fluorodeoxyglucose (FDG) has become a prominent part of the workup at diagnosis and during follow-up. Recently, PET has been integrated in the revised response criteria for malignant lymphoma.