Somatostatin Receptor Imaging with [18F]FET-ßAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study.

There is a clinical need for 18F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [68Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [18F]fluoroethyl-triazole-[Tyr3]-octreotate ([18F]FET-ßAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [18F]FET-ßAG-TOCA PET/CT compared with [68Ga]Ga-DOTA- peptide PET/CT in patients with NET. Methods: Forty-five patients with histologically confirmed NET, grades 1 and 2, underwent PET/CT imaging with both [18F]FET-ßAG-TOCA and [68Ga]Ga-peptide performed within a 6-mo window (median, 77 d; range, 6-180 d). Whole-body PET/CT was conducted 50 min after injection of 165 MBq of [18F]FET-ßAG-TOCA. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios at both lesion and regional levels by 2 unblinded, experienced readers. A randomized, blinded reading of both scans was also then undertaken by 3 experienced readers, and consensus was assessed at a regional level. The ability of both tracers to visualize liver metastases was also assessed. Results: A total of 285 lesions were detected on both imaging modalities. An additional 13 tumor deposits were seen in 8 patients on [18F]FET-ßAG-TOCA PET/CT, and [68Ga]Ga-DOTA-peptide PET/CT detected an additional 7 lesions in 5 patients. Excellent correlation in SUVmax was observed between both tracers (r = 0.91; P < 0.001). No difference was observed between median SUVmax across regions, except in the liver, where the median tumor-to-background ratio of [18F]FET-ßAG-TOCA was significantly lower than that of [68Ga]Ga-DOTA-peptide (2.5 ± 1.9 vs. 3.5 ± 2.3; P < 0.001). Conclusion: [18F]FET-ßAG-TOCA was not inferior to [68Ga]Ga-DOTA-peptide in visualizing NET and may be considered in routine clinical practice given the longer half-life and availability of the cyclotron-produced fluorine radioisotope.

Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH).

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12-16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study.

PURPOSE: MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study. METHODS: Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade - LGG - and higher-grade - HGG - patients). FPIA was injected as an intravenous bolus injection (range 342-368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min. RESULTS: All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG. CONCLUSION: Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04097535.

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-ßAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).

Comprehensive Diagnosis and Management of POEMS Syndrome.

Polyneuropathy Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome is a rare multisystem condition with a range of manifestations which are often overlooked as trivial comorbidities, until their whole triggers the possibility of the diagnosis. The diagnosis is typically delayed by 12-16 months, by which time patients can be severely disabled. There are no established consensus guidelines. We provide clinicians a comprehensive blueprint for managing POEMS from diagnostic suspicion through the work-up, selection of therapy, follow-up, and treatment of relapse based on published evidence and our large single-center experience. A multidisciplinary approach is essential including expert hematologists, neurologists, histopathologists, radiologists, and neurophysiologists. The aim of treatment is to eradicate the underlying plasma cell dyscrasia, but there are limited trial data to guide treatment decisions. Supportive care considerations include management of endocrinopathy, neuropathy, thrombosis, and infection. Response assessment is centered on clinical, neuropathy, hematological, vascular endothelial growth factor, and radiological criteria. Future clinical trials are welcomed in this setting where evidence is limited.

Consideration of Metabolite Efflux in Radiolabelled Choline Kinetics.

Hypoxia is a complex microenvironmental condition known to regulate choline kinase α (CHKA) activity and choline transport through transcription factor hypoxia-inducible factor-1α (HIF-1α) and, therefore, may confound the uptake of choline radiotracer [18F]fluoromethyl-[1,2-2H4]-choline ([18F]-D4-FCH). The aim of this study was to investigate how hypoxia affects the choline radiotracer dynamics. Three underlying mechanisms by which hypoxia could potentially alter the uptake of the choline radiotracer, [18F]-D4-FCH, were investigated: 18F-D4-FCH import, CHKA phosphorylation activity, and the efflux of [18F]-D4-FCH and its phosphorylated product [18F]-D4-FCHP. The effects of hypoxia on [18F]-D4-FCH uptake were studied in CHKA-overexpressing cell lines of prostate cancer, PC-3, and breast cancer MDA-MB-231 cells. The mechanisms of radiotracer efflux were assessed by the cell uptake and immunofluorescence in vitro and examined in vivo (n = 24). The mathematical modelling methodology was further developed to verify the efflux hypothesis using [18F]-D4-FCH dynamic PET scans from non-small cell lung cancer (NSCLC) patients (n = 17). We report a novel finding involving the export of phosphorylated [18F]-D4-FCH and [18F]-D4-FCHP via HIF-1α-responsive efflux transporters, including ABCB4, when the HIF-1α level is augmented. This is supported by a graphical analysis of human data with a compartmental model (M2T6k + k5) that accounts for the efflux. Hypoxia/HIF-1α increases the efflux of phosphorylated radiolabelled choline species, thus supporting the consideration of efflux in the modelling of radiotracer dynamics.

Clinical Translation of Positive Metastases Identified on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging in the Management of De Novo Synchronous Oligometastatic Prostate Cancer.

Recent evidence from randomised trials supports the diagnostic superiority of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) over conventional imaging in the detection of distant occult metastasis in men with newly diagnosed high-risk prostate cancer. This may result in a rise in the detection of de novo synchronous hormone-sensitive "oligometastatic" prostate cancer. We outline the evidence supporting PSMA PET/CT imaging in primary staging. We also discuss the translation of positive areas with a high probability of distant metastasis into clinical therapeutic targets for metastasis-directed interventions. Finally, we highlight the role of PSMA PET/CT as an imaging biomarker. This may have future utility in disease monitoring and prediction of response to systemic, local cytoreductive and metastasis-directed interventions. PATIENT SUMMARY: A new whole-body scan can accurately detect cancer deposits in men in whom distant prostate cancer spread is suspected. This may be useful for monitoring and predicting response to drug therapy, treatments to the prostate, and cancer deposits.

Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline.

Purpose: The spatio-molecular distribution of choline and its metabolites in tumors is highly heterogeneous. Due to regulation of choline metabolism by hypoxic transcriptional signaling and other survival factors, we envisage that detection of such heterogeneity in patient tumors could provide the basis for advanced localized therapy. However, non-invasive methods to assess this phenomenon in patients are limited. We investigated such heterogeneity in Non-Small Cell Lung Cancer (NSCLC) with [18F]fluoromethyl-(1,2-2H4) choline ([18F]D4-FCH) and positron emission tomography/computed tomography (PET/CT). Experimental design: [18F]D4-FCH (300.5±72.9MBq [147.60-363.6MBq]) was administered intravenously to 17 newly diagnosed NSCLC patients. PET/CT scans were acquired concurrently with radioactive blood sampling to permit mathematical modelling of blood-tissue transcellular rate constants. Comparisons were made with biopsy-derived choline kinase-α (CHKα) expression and diagnostic [18F]fluorodeoxyglucose ([18F]FDG) scans. Results: Oxidation of [18F]D4-FCH to [18F]D4-fluorobetaine was suppressed (48.58±0.31% parent at 60 min) likely due to the deuterium isotope effect embodied within the design of the radiotracer. Early (5 min) and late (60 min) images showed specific uptake of tracer in all 51 lesions (tumors, lymph nodes and metastases) from 17 patients analyzed. [18F]D4-FCH-derived uptake (SUV60max) in index primary lesions (n=17) ranged between 2.87-10.13; lower than that of [18F]FDG PET [6.89-22.64]. Mathematical modelling demonstrated net irreversible uptake of [18F]D4-FCH at steady-state, and parametric mapping of the entire tumor showed large intratumorally heterogeneity in radiotracer retention, which is likely to have influenced correlations with biopsy-derived CHKα expression. Conclusions: [18F]D4-FCH is detectable in NSCLC with large intratumorally heterogeneity, which could be exploited in the future for targeting localized therapy.

Monitoring Response to Transarterial Chemoembolization in Hepatocellular Carcinoma Using 18F-Fluorothymidine PET.

Accurate disease monitoring is essential after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) because of the potential for profound adverse events and large variations in survival outcome. Posttreatment changes on conventional imaging can confound determination of residual or recurrent disease, magnifying the clinical challenge. On the basis of increased expression of thymidylate synthase (TYMS), thymidine kinase 1 (TK-1), and equilibrative nucleoside transporter 1 (SLC29A1) in HCC compared with liver tissue, we conducted a proof-of-concept study evaluating the efficacy of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET to assess response to TACE. Because previous PET studies in HCC have been hampered by high background liver signal, we investigated whether a temporal-intensity voxel clustering (kinetic spatial filtering, or KSF) improved lesion detection. Methods: A tissue microarray was built from 36 HCC samples and from matching surrounding cirrhotic tissue and was stained for TK-1 A prospective study was conducted; 18 patients with a diagnosis of HCC by the criteria of the American Association for the Study of Liver Diseases who were eligible for treatment with TACE were enrolled. The patients underwent baseline conventional imaging and dynamic 18F-FLT PET with KSF followed by TACE. Imaging was repeated 6-8 wk after TACE. The PET parameters were compared with modified enhancement-based RECIST. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1, and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC (P < 0.05). The sensitivity of 18F-FLT PET for baseline HCC detection was 73% (SUVmax, 9.7 ± 3.0; tumor to liver ratio, 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response after TACE by modified RECIST was 58% (14 patients with 24 lesions). A 30% reduction in mean 18F-FLT PET uptake was observed after TACE, correlating with an observed PET response of 60% (15/25). A significant and profound reduction in the radiotracer delivery parameter K1 after TACE was observed. Conclusion:18F-FLT PET can differentiate HCC from surrounding cirrhotic tissue, with PET parameters correlating with TACE response. KSF did not improve visualization of tumor lesions. These findings warrant further investigation.

[18F]FET-ßAG-TOCA: The Design, Evaluation and Clinical Translation of a Fluorinated Octreotide.

The success of Lutathera™ ([177Lu]Lu-DOTA-TATE) in the NETTER-1 clinical trial as a peptide receptor radionuclide therapy (PRRT) for somatostatin receptor expressing (SSTR) neuroendocrine tumours (NET) is likely to increase the demand for patient stratification by positron emission tomography (PET). The current gold standard of gallium-68 radiolabelled somatostatin analogues (e.g., [68Ga]Ga-DOTA-TATE) works effectively, but access is constrained by the limited availability and scalability of gallium-68 radiopharmaceutical production. The aim of this review is three-fold: firstly, we discuss the peptide library design, biological evaluation and clinical translation of [18F]fluoroethyltriazole-ßAG-TOCA ([18F]FET-ßAG-TOCA), our fluorine-18 radiolabelled octreotide; secondly, to exemplify the potential of the 2-[18F]fluoroethylazide prosthetic group and copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry in accessing good manufacturing practice (GMP) compatible radiopharmaceuticals; thirdly, we aim to illustrate a framework for the translation of similarly radiolabelled peptides, in which in vivo pharmacokinetics drives candidate selection, supported by robust radiochemistry methodology and a route to GMP production. It is hoped that this review will continue to inspire the development and translation of fluorine-18 radiolabelled peptides into clinical studies for the benefit of patients.

Clinical translation of 18F-fluoropivalate - a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers.

BACKGROUND: Fatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions. MATERIALS AND METHODS: Healthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31-164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1. RESULTS: All subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects, though systemic NEFA and carnitine levels reflected fasted and fed states. CONCLUSION: The favourable safety, imaging, and dosimetric profile makes 18F-FPIA a promising candidate radiotracer for tracing SCFA metabolism.

Immunotherapy-related adverse effects on 18F-FDG PET/CT imaging.

18F-Fluorodeoxyglucose positron emission tomography/CT imaging plays a key role in oncological imaging including in staging, radiotherapy planning, treatment response and recurrence assessment. Immunotherapies represent a major advance in cancer therapy for a number of tumours with resulting survival benefit. However, a wide range of immune related adverse events (irAEs), some of which can be apparent on imaging, have been reported. These involve many organ systems but particularly endocrine, cutaneous and gastrointestinal systems. Early detection of irAEs is essential to aid diagnosis and management of patients and to reduce associated morbidity. In addition, it is important to not mistake treatment related effects for disease.This pictorial review aims to identify common irAEs and changes seen on 18F-fluorodeoxyglucose positron emission tomography/CT.

[18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer.

BACKGROUND: Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αvß3 and αvß5 are both upregulated in tumor-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvß3/5, and was used to assess the anti-angiogenic effect of pazopanib. PATIENTS AND METHODS: We conducted an open-label, phase Ib study in patients with platinum-resistant/refractory ovarian cancer. Patients received 1 week of single-agent pazopanib (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m2). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [18F]fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities, and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. RESULTS: Fourteen patients were included in the intention-to-treat analysis. Complete and partial responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [18F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K1 and Ki following pazopanib indicating reduced radioligand delivery and retention. CONCLUSIONS: Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [18F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti-angiogenic response.

Clinical PET Imaging in Prostate Cancer.

Prostate cancer is the second most common cancer in men worldwide, with a wide spectrum of biologic behavior ranging from indolent low-risk disease to highly aggressive castration-resistant prostate cancer. Conventional imaging with computed tomography, magnetic resonance imaging, and bone scintigraphy is limited for the detection of nodal disease and distant bone metastases. In addition, advances in the available therapeutic options, both localized and systemic, drive the requirement for precise diagnostic and prognostic tools to refine the individual therapeutic approach at various times in the management of patients with prostate cancer. Positron emission tomography (PET) has a rapidly evolving role in the assessment of prostate cancer, particularly in the scenario of biochemical relapse. Fluorine 18 (18F) fluorodeoxyglucose, the most widely available PET tracer, has limitations, particularly in indolent prostate cancer. In the past decade, several PET tracers with specific molecular targets have reached the clinical domain. These tracers include 18F-sodium fluoride, which is a bone-specific biomarker of osteoblastic activity; 18F-choline and carbon 11-choline, which are directed at cell membrane metabolism; gallium 68-prostate-specific membrane antigen ligands; and, more recently, an amino acid analog, 18F-fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid; also known as FACBC), which is also directed at cell membrane turnover. The mechanisms of actions of the clinically available PET tracers are reviewed, as well as their role in the imaging of prostate cancer with reference to relevant guidelines and the technical and imaging pearls and pitfalls of these tracers. ©RSNA, 2017.

Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors.

UNLABELLED: We conducted the first-in-human study of (18)F-fluoroethyl triazole [Tyr(3)] octreotate ((18)F-FET-ßAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. METHODS: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of (18)F-FET-ßAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed whole-body PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. RESULTS: All patients tolerated (18)F-FET-ßAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. CONCLUSION: The favorable safety, imaging, and dosimetric profile makes (18)F-FET-ßAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.

The emerging role of positron emission tomography in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. HCC a heterogeneous disease occurring on the background of cirrhosis. The presence of cirrhosis limits the sensitivity of conventional imaging modalities in differentiating HCC from surrounding cirrhotic parenchyma. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is widely used for assessing a variety of malignancies, however, has poor sensitivity in the evaluation of HCC. This has led to the investigation of other radiotracers such as 11C-acetate and 11C-choline, with improved sensitivity in terms of detection and therapeutic response. In this review, we discuss the emerging field of PET imaging for the detection, staging and assessment of treatment response in HCC. In particular we discuss the role of 18F-FDG-PET in imaging hepatocellular cancer, the limitations of this PET tracer and emerging novel PET tracers being investigated that exploit key metabolic processes including fatty acid and lipid synthesis, choline kinase activity and gene expression.

Bladder conservation for muscle-invasive bladder cancer.

In the UK alone, approximately 10,000 patients are diagnosed with bladder cancer each year. Of these, muscle-invasive bladder cancer stage T2 or T3 accounts for 10-15%, with the remainder being non-muscle-invasive tumors, dealt with by local intravesical treatment. This group of patients are often older, the median age at presentation being 65-70 years and since this is a smoking-associated cancer there are often significant comorbidities. Transitional cell carcinoma is the most common histological type and comprises >90% of bladder cancers. Other cell types include squamous cell carcinoma, adenocarcinoma, small-cell carcinoma, sarcoma, carcinosarcoma, lymphoma and melanoma. In bladder cancer, the most important prognostic factors are stage and grade. Cystectomy, radiotherapy and chemotherapy all have a role in the management of bladder cancer. In many centers across the world, the standard management of muscle-invasive bladder cancer, stage T2 and T3, is radical cystectomy and pelvic lymphadenectomy. There is now increasing evidence that modern nonsurgical approaches using chemoradiation achieve results at least as good as those with surgery and enable bladder preservation in the majority of patients. Optimal chemoradiation schedules and the role of radiosensitizers remain important areas of research to optimize the bladder-preserving approach. Ultimately, a prospective randomized trial is needed to compare modern state-of-the-art surgery with chemoradiation to provide high-level evidence on which informed patient choices can be made.