Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.

18F-fluorocholine PET/CT detects parathyroid gland hyperplasia as well as adenoma: 401 PET/CTs in one center.

BACKGROUND: During the past decade, 18F-fluorocholine (FCH) PET/CT has been continuously performed at Tenon Hospital (Paris, France) for the detection of hyperfunctioning parathyroid glands (PT). METHODS: A cohort of 401 patients, deliberately referred for HPT since September 2012, has been analyzed. The aim of this real-life retrospective study was to determine the diagnostic utility of FCH in this setting, overall and in subgroups according to the type of hyperparathyroidism (HPT), the context of FCH in the imaging work-up and in the patient's history: initial imaging or persistence or recurrence after previous parathyroidectomy (PTX). The influence of the histologic type of resected PTs, hyperplasia or adenoma, on the preoperatory detection on FCH PET/CT has been studied as well. RESULTS: Four hundred one FCH PET/CTs were included in the cohort, performed in 323 patients with primary HPT (pHPT), including 18 with familial HPT (fHPT), and in 78 patients with secondary renal HPT (rHPT). The overall positivity rate in the 401 FCH PET/CTs was 73%. The PTX rate was twice greater in patients whose FCH PET/CT was positive than negative (73% vs. 35%). Abnormal PT(s) were pathology proven in 214 patients: only hyperplastic gland(s) in 75 cases and at least one adenoma in 136 cases; FCH PET/CT sensitivity was 89% and 92%, respectively. Similarly, there was no significant difference in patient-based sensitivity whether FCH PET/CT was performed as 1st line or later in the imaging work-up, or indicated for initial imaging or for suspicion of persistent or recurrent HPT. Gland-based sensitivity was significantly lower for hyperplasia than for adenoma (72% and 86%, respectively). The lowest gland-based sensitivity value was 65%, observed in case of hyperplasia and when FCH was performed late in the imaging work-up. FCH PET/CT correctly showed multiglandular HPT (MGD) in 36/61 proven cases, 59%. Results of ultrasonography (US) and 99mTc-sestaMIBI (MIBI) imaging were available in 346 and 178 patients, respectively. For both modalities, the corresponding sensitivity values were significantly less than those of FCH PET/CT (e.g., overall gland-based sensitivity 78% for FCH, 45% for US, 30% for MIBI) and MGD was detected in 32% of cases by US and 15% by MIBI. CONCLUSIONS: Although FCH PET/CT has been performed since 2017 as 1st line imaging for HPT at Tenon Hospital (Paris, France), a large majority of patients underwent prior US and/or MIBI in their preoperative work-up. Therefore, a selection bias is very likely, as most patients referred to FCH PET/CT had non-conclusive or discordant results of US and MIBI, explaining the low performance of those modalities in the present cohort compared to published results. Nevertheless, the superiority of FCH PET/CT over US and MIBI in detecting abnormal PTs reported in various comparative studies is definitely confirmed in this larger real-life cohort. The detection with FCH PET/CT of hyperplastic PTs was somewhat lower than that of adenomas but was better than using US or MIBI. The present results lead to recommend FCH PET/CT as the first line imaging modality in HPT when it is widely available or, if less available, at least in HPT with predominance of hyperplasia and/or MGD.

An essential practice summary of the new EANM guidelines for parathyroid imaging.

Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.

Multiple endocrine neoplasia type 1 or 4: detection of hyperfunctioning parathyroid glands with 18F-fluorocholine PET/CT. Illustrative cases and pitfalls.

18F-fluorocholine (FCH) PET/CT is now well established to detect the hyperfunctioning parathyroid glands (HFPTG) in a case of sporadic primary hyperparathyroidism (pHPT), but only limited evidence is available about the utility of FCH PET/CT to detect the HFPTG in patients with multiple endocrine neoplasia (MEN) type 1 or 4. The pHPT in this context frequently consists in a multiglandular disease with small hyperplastic glands rather than adenomas, which is challenging for imaging modalities. The data of patients with MEN1 or MEN4 after parathyroidectomy referred to FCH PET/CT for presurgical localization of HFPTG were retrospectively reviewed, including follow-up after parathyroidectomy, in search for diagnostic performance and for potential pitfalls. In the present cohort, 16 patients referred to FCH PET/CT as part of their initial pHPT work-up were subsequently operated, 44 abnormal parathyroid glands (PT) were resected, of which 32 (73%) had been detected on FCH PET/CT and 2 considered as equivocal foci. Nine patients referred to FCH PET/CT for recurrent pHPT who were subsequently operated, 14 abnormal PT were resected, all had been detected on FCH PET/CT. FCH PET/CT permitted a unilateral approach for PTx in 4 of them. In one patient with MEN4 and pHPT, the HFPTG could not be visualized on FCH PET/CT but was localized by ultrasonography. Several causes of false positive or false negative results, incidental finding and pitfalls are listed and discussed. FCH PET/CT has a positive benefit/risk ratio in the detection of HFPTG in case of MEN1 (the data in MEN4 being currently very limited) with the most effective detection rate of current imaging modalities for HFPTG, few pitfalls, and an adequate impact on patient management compared to sesta MIBI SPECT and ultrasonography.

Survey by the French Medicine Agency (ANSM) of the imaging protocol, detection rate, and safety of 68Ga-PSMA-11 PET/CT in the biochemical recurrence of prostate cancer in case of negative or equivocal 18F-fluorocholine PET/CT: 1084 examinations.

INTRODUCTION: Despite growing evidence of a superior diagnostic performance of 68Ga-PSMA-11 over 18F-fluorocholine (FCH) PET/CT, the number of PET/CT centres able to label on site with gallium-68 is still currently limited. Therefore, patients with biochemical recurrence (BCR) of prostate cancer frequently undergo FCH as the 1st-line PET/CT. Actually, the positivity rate (PR) of a second-line PSMA-11 PET/CT in case of negative FCH PET/CT has only been reported in few short series, in a total of 185 patients. Our aims were to check (1) whether the excellent PR reported with PSMA-11 is also obtained in BCR patients whose recent FCH PET/CT was negative or equivocal; (2) in which biochemical and clinical context a high PSMA-11 PET/CT PR may be expected in those patients, in particular revealing an oligometastatic pattern; (3) whether among the various imaging protocols for PSMA-11 PET/CT used in France, one yields a significantly highest PR; (4) the tolerance of PSMA-11. PATIENTS AND METHODS: Six centres performed 68Ga-PSMA-11 PET/CTs during the first 3 years of its use in France. Prior to each PET/CT, the patient's data were submitted prospectively for authorisation to ANSM, the French Medicine Agency. The on-site readings of 1084 PSMA-11 PET/CTs in BCR patients whose recent FCH PET/CTs resulted negative or equivocal were pooled and analysed. RESULTS: (1) The overall PR was 68%; for a median serum PSA level (sPSA) of 1.7 ng/mL, an oligometastatic pattern (1-3 foci) was observed in 31% of the cases overall; (2) PR was significantly related to sPSA (from 41% if < 0.2 ng/mL to 81% if ≥ 2 ng/mL), to patients' age, to initial therapy (64% if prostatectomy vs. 85% without prostatectomy due to frequent foci in the prostate fossa), to whether FCH PET/CT was negative or equivocal (PR = 62% vs. 82%), and to previous BCR (PR = 63% for 1st BCR vs. 72% in case of previous BCR); (3) no significant difference in PR was found according to the imaging protocol: injected activity, administration of a contrast agent and/or of furosemide, dose length product, one single or multiple time points of image acquisition; (4) no adverse event was reported after PSMA-11 injection, even associated with a contrast agent and/or furosemide. CONCLUSION: Compared with the performance of PSMA-11 PET/CT in BCR reported independently of FCH PET/CT in 6 large published series (n > 200), the selection based on FCH PET/CT resulted in no difference of PSMA-11 PR for sPSA < 1 ng/mL but in a slightly lower PR for sPSA ≥ 1 ng/mL, probably because FCH performs rather well at this sPSA and very occult BCR was over-represented in our cohort. An oligometastatic pattern paving the way to targeted therapy was observed in one fourth to one third of the cases, according to the clinico-biochemical context of the BCR. Systematic dual or triple acquisition time points or administration of a contrast agent and/or furosemide did not bring a significant added value for PSMA-11 PET/CT positivity and should be decided on individual bases.

The EANM practice guidelines for parathyroid imaging.

INTRODUCTION: Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration. METHODS: Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT. CONCLUSION: These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.

Patient external dose rate after 177Lu-DOTATATE therapy: factors affecting its decrease and predictive value.

Rationale: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE (oxodotreotide) results in external radiation exposure from the patient. In the PREELU observational prospective study, we determined the equivalent dose rate at 1 m of the patient (EDR-1m) for a period following PRRT. The main objective was to predict which patients could be discharged from the hospital at approximately 3 h after the administration of 177Lu-DOTATATE, i.e. at the end of the infusion of amino-acids according to our PRRT protocol. As presenting no undue risk of radiation exposure for the public, those patients could be treated as outpatients or day patients, rather than inpatients. Methods: We sequentially measured EDR-1m facing the sternum and then the pelvis during 50 PRRT in 24 patients with metastatic neuroendocrine tumours, each 30 minutes after ending administration of Lutathera, over at least 180 minutes. Results: 180 minutes after the administration of ca. 7400 MBq of Lutathera, EDR-1m was <40 µSv/h in all cases, and <25 µSv/h in 32 cases (64%). After an overnight hospital stay, EDR-1m was <25 µSv/h in all cases. The EDR-1m value measured facing the sternum was the greatest in about one-fourth of paired measurements. In patients whose creatinine clearance was >96 mL/min/1.73m2, the EDR-1m was most likely (predictive value=90%) to drop below 25 µSv/h within 180 minutes after the administration of Lutathera. In 16 patients who benefited from several PRRT cycles, the creatinine clearance did not decrease significantly from one cycle to the next, probably due to the kidney protection by the amino-acid infusion. The patients whose EDR-1m dropped below 25 µSv/h at 180 minutes during their first PRRT cycle were unlikely (predictive value= 88%) to decease during the following two years. Conclusion: All patients could have been discharged 3 h after administration according to the criterion EDR-1m <40 µSv/h. Using EDR-1m <25 µSv/h as criterion, an extended hospital stay beyond 3 h would have been necessary in around one-third of the PRRT treatments and could be anticipated based on creatinine clearance ≤96 mL/min/1.73m2. EDR-1m <25 µSv/h at 180 min during the first PRRT yielded a strong predictive value on the patient's survival at two years, a finding that should be confirmed in future studies.

Hepatocellular Carcinomas With Mutational Activation of Beta-Catenin Require Choline and Can Be Detected by Positron Emission Tomography.

BACKGROUND & AIMS: In one-third of hepatocellular carcinomas (HCCs), cancer cells have mutations that activate ß-catenin pathway. These cells have alterations in glutamine, bile, and lipid metabolism. We investigated whether positron emission tomography (PET) imaging allows identification of altered metabolic pathways that might be targeted therapeutically. METHODS: We studied mice with activation of ß-catenin in liver (Apcko-liv mice) and male C57Bl/6 mice given injections of diethylnitrosamine, which each develop HCCs. Mice were fed a conventional or a methionine- and choline-deficient diet or a choline-deficient (CD) diet. Choline uptake and metabolism in HCCs were analyzed by micro-PET imaging of mice; livers were collected and analyzed by histologic, metabolomic, messenger RNA quantification, and RNA-sequencing analyses. Fifty-two patients with HCC underwent PET imaging with 18F-fluorodeoxyglucose, followed by 18F-fluorocholine tracer metabolites. Human HCC specimens were analyzed by immunohistochemistry, quantitative polymerase chain reaction, and DNA sequencing. We used hepatocytes and mouse tumor explants for studies of incorporation of radiolabeled choline into phospholipids and its contribution to DNA methylation. We analyzed HCC progression in mice fed a CD diet. RESULTS: Livers and tumors from Apcko-liv mice had increased uptake of dietary choline, which contributes to phospholipid formation and DNA methylation in hepatocytes. In patients and in mice, HCCs with activated ß-catenin were positive in 18F-fluorocholine PET, but not 18F-fluorodeoxyglucose PET, and they overexpressed the choline transporter organic cation transporter 3. The HCC cells from Apcko-liv mice incorporated radiolabeled methyl groups of choline into phospholipids and DNA. In Apcko-liv mice, the methionine- and choline-deficient diet reduced proliferation and DNA hypermethylation of hepatocytes and HCC cells, and the CD diet reduced long-term progression of tumors. CONCLUSIONS: In mice and humans, HCCs with mutations that activate ß-catenin are characterized by increased uptake of a fluorocholine tracer, but not 18F-fluorodeoxyglucose, revealed by PET. The increased uptake of choline by HCCs promotes phospholipid formation, DNA hypermethylation, and hepatocyte proliferation. In mice, the CD diet reverses these effects and promotes regression of HCCs that overexpress ß-catenin.

18F-fluorocholine PET/CT in MEN1 Patients with Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (HPT1) is the most frequent endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Its surgical management is challenging. We aimed to describe and compare the imaging findings of parathyroid ultrasound (US), sestaMIBI scintigraphy (sestaMIBI), and 18F-fluorocholine (FCH) PET/CT in a series of MEN1 patients with HPT1. METHODS: Retrospective analysis of a cohort of MEN1 patients with HPT1 assessed by parathyroid US, sestaMIBI scintigraphy and SPECT/CT, and FCH-PET/CT for potential surgery between 2015 and 2019. RESULTS: Twenty-two patients with a confirmed diagnosis of MEN1 who presented with HPT1 and were assessed by the 3 imaging modalities were included. After imaging workups, 11 patients were operated on for the first time, 4 underwent a redo surgery, and 7 did not undergo an operation. The overall patient-based positivity rate of imaging was 91% (20 of 22) for parathyroid US and 96% (21 of 22) for both sestaMIBI and FCH-PET/CT. The 3 imaging modalities demonstrated negative findings in 1/22 patient who did not undergo surgery. Overall, 3 pathologic glands were not detected by any imaging technique. SestaMIBI and FCH-PET/CT both resulted in the same 3 false-positive results in ectopic areas with a significant uptake on two thymic carcinoid tumors and one inflammatory lymph node. FCH-PET/CT provided more surgically relevant data than sestaMIBI in 4/11 patients with initial surgery and in 1/4 patient who underwent redo surgery. CONCLUSIONS: Compared to sestaMIBI scintigraphy, FCH-PET/CT provides additional information regarding the number of pathologic parathyroid glands and their localization in MEN1 patients with HPT1.

Comparison of 18F-sodium fluoride PET/CT, 18F-fluorocholine PET/CT and diffusion-weighted MRI for the detection of bone metastases in recurrent prostate cancer: a cost-effectiveness analysis in France.

BACKGROUND: The diagnostic performance of 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18F-fluorocholine PET/CT (FCH) and diffusion-weighted whole-body magnetic resonance imaging (DW-MRI) in detecting bone metastases in prostate cancer (PCa) patients with first biochemical recurrence (BCR) has already been published, but their cost-effectiveness in this indication have never been compared. METHODS: We performed trial-based and model-based economic evaluations. In the trial, PCa patients with first BCR after previous definitive treatment were prospectively included. Imaging readings were performed both on-site by local specialists and centrally by experts. The economic evaluation extrapolated the diagnostic performances of the imaging techniques using a combination of a decision tree and Markov model based on the natural history of PCa. The health states were non-metastatic and metastatic BCR, non-metastatic and metastatic castration-resistant prostate cancer and death. The state-transition probabilities and utilities associated with each health state were derived from the literature. Real costs were extracted from the National Cost Study of hospital costs and the social health insurance cost schedule. RESULTS: There was no significant difference in diagnostic performance among the 3 imaging modalities in detecting bone metastases. FCH was the most cost-effective imaging modality above a threshold incremental cost-effectiveness ratio of 3000€/QALY when imaging was interpreted by local specialists and 9000€/QALY when imaging was interpreted by experts. CONCLUSIONS: FCH had a better incremental effect on QALY, independent of imaging reading and should be preferred for detecting bone metastases in patients with biochemical recurrence of prostate cancer. TRIAL REGISTRATION: NCT01501630. Registered 29 December 2011.

Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis.

Neurotensin receptor 1 (NTSR1) is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Specific noninvasive positron-emission tomography (PET) imaging probes may improve the diagnostic accuracy and the monitoring of therapy for patients with PDAC. Here, we report the use of the 68Ga-labeled neurotensin (NTS) analogue DOTA-NT-20.3 to image human PDAC in animal models and to discriminate tumors from pancreatitis. In addition to the preclinical study, two tissue microarray slides, constructed by small core biopsies (2-5) from standard paraffin-embedded tumor tissues, were used to confirm the high (78%) positivity rate of NTSR1 expression in human PDAC. PET imaging, biodistribution, blocking, and histology studies were performed in subcutaneous AsPC-1 pancreatic tumor-bearing mice. 68Ga-DOTA-NT-20.3 PET images showed rapid tumor uptake and high contrast between the tumor and background with a fast blood clearance and a moderate accumulation in the kidneys. Ex vivo biodistribution showed low uptake in normal pancreas (0.22% IA/g) and in the remaining organs at 1 h postinjection, kidney retention (5.38 ± 0.54% IA/g), and fast clearance from blood and confirmed high uptake in tumors (5.28 ± 0.93% IA/g), leading to a tumor-to-blood ratio value of 6 at 1 h postinjection. The significant decrease of tumor uptake in a blocking study demonstrated the specificity of 68Ga-DOTA-N-T20.3 to target NTSR1 in vivo. PET imaging was also conducted in an orthotopic xenograft model that allows tumors to grow in their native microenvironment and in an experimental pancreatitis model generated by caerulein injections. As opposed to 2-[18F]fluoro-deoxyglucose, 68Ga-DOTA-NT-20.3 distinguishes PDAC from pancreatitis. Thus, 68Ga-DOTA-NT-20.3 is a promising PET imaging probe for imaging PDAC in humans.

Impact of sodium 18F-fluoride PET/CT, 18F-fluorocholine PET/CT and whole-body diffusion-weighted MRI on the management of patients with prostate cancer suspicious for metastasis: a prospective multicentre study.

PURPOSE: To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis. METHODS: Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test. RESULTS: One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p < 0.0001) and highest (41%) for FCH-PET/CT at BCR. Actual management was adequate in all patients but two. CONCLUSIONS: Whole-body imaging induced a change in management in approximately a third of PCa patients suspicious for metastasis. The impact rate was determined to be greatest at first BCR using FCH-PET/CT. NaF-PET/CT and DW-MRI seemed less useful in this context.

Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies.

Diagnostic performance and impact on patient management of 68Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours.

PURPOSE: Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, 68Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of 68Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management. METHODS: 68Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The 68Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up. RESULTS: 68Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. 68Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. 68Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, 68Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous 111In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of 68Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of 68Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23. CONCLUSION: 68Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.

Editorial Comment: Advances in MRI and PET of the prostate: concurrence or complementarity?

This Editorial Comment refers to the articles "Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population" by Barrett T et al., Eur Radiol. 2017 Dec 8 and "18F-Fluciclovine PET/MRI for preoperative lymph node staging in high-risk prostate cancer patients" by Selnæs KM et al., Eur Radiol. 2018 Jan 2.

Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

OBJECTIVES: To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe1-Tyr3-octreotide labelled with gallium-68 (68Ga-DOTA-TOC). METHODS: In 535 NET patients, 68Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUVmax) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. RESULTS: In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm3, SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. CONCLUSIONS: The high sensitivity of 68Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68Ga-DOTA-TOC uptake. KEY POINTS: • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

Liposomes for PET and MR Imaging and for Dual Targeting (Magnetic Field/Glucose Moiety): Synthesis, Properties, and in Vivo Studies.

We describe the potentiality of a new liposomal formulation enabling positron emission tomography (PET) and magnetic resonance MR() imaging. The bimodality is achieved by coupling a 68Ga-based radiotracer on the bilayer of magnetic liposomes. In order to enhance the targeting properties obtained under a permanent magnetic field, a sugar moiety was added in the lipid formulation. Two new phospholipids were synthesized, one with a specific chelator of 68Ga (DSPE-PEG-NODAGA) and one with a glucose moiety (DSPE-PEG-glucose). The liposomes were produced according to a fast and safe process, with a high radiolabeling yield. MR and PET imaging were performed on mice bearing human glioblastoma tumors (U87MG) after iv injection. The accumulation of the liposomes in solid tumor is evidenced by MR imaging and the amount is evaluated in vivo and ex vivo according to PET imaging. An efficient magnetic targeting is achieved with these new magnetic liposomes.

18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study.

PURPOSE: Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. METHODS: We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). RESULTS: In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. CONCLUSIONS: These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG.