Real-world experience with 11C-methionine positron emission tomography in the management of acromegaly.

BACKGROUND: L-[methyl-11C]-methionine-positron emission tomography (Met-PET) is a potentially important imaging adjunct in the diagnostic workup of pituitary adenomas, including somatotroph tumors. Met-PET can identify residual or occult disease and make definitive therapies accessible to a subgroup of patients who would otherwise require lifelong medical therapy. However, existing data on its use are still limited to small case series. Here, we report the largest single-center experience (n = 61) in acromegaly. METHODS: A total of 189 cases of acromegaly were referred to our national Met-PET service in the last 12 years. For this analysis, we have reviewed outcomes in those 61 patients managed exclusively by our multidisciplinary team (single center, single surgeon). Referral indications were as follows: indeterminate magnetic resonance imaging (MRI; n = 38, 62.3%), occult residual (n = 14, 23.0%), (radio-)surgical planning (n = 6, 9.8%), and occult de novo tumor (n = 3, 4.9%). RESULTS: A total of 33/61 patients (54.1%) underwent PET-guided surgery. Twenty-four of 33 patients (72.7%) achieved complete biochemical remission following (re-)surgery. Insulin-like growth factor 1 levels were reduced to <2 × upper limit of normal (ULN) in 6 of the remaining 9 cases, 3 of whom achieved levels of <1.1 × ULN compared with mean preoperative levels of 2.4 × ULN (SD 0.8) for n = 9. Only 3 patients developed single new hormonal deficits (gonadotropic/thyrotropic insufficiency). There were no neurovascular complications after surgery. CONCLUSION: In patients with persistent/recurrent acromegaly or occult tumors, Met-PET can facilitate further targeted intervention (surgery/radiosurgery). This led to complete remission in most cases (24/33) or significant improvement with comparatively low risk of complications. L-[methyl-11C]-methionine-positron emission tomography should therefore be considered in all patients who are potential candidates for further surgical intervention but present no clear target on MRI.

Diagnostic utility of 11 C-methionine PET/CT in primary hyperparathyroidism in a UK cohort: A single-centre experience and literature review.

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

Clinical Utility of 18Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) in Multivisceral Transplant Patients.

Multivisceral transplant (MVTx) refers to a composite graft from a cadaveric donor, which often includes the liver, the pancreaticoduodenal complex, and small intestine transplanted en bloc. It remains rare and is performed in specialist centres. Post-transplant complications are reported at a higher rate in multivisceral transplants because of the high levels of immunosuppression used to prevent rejection of the highly immunogenic intestine. In this study, we analyzed the clinical utility of 28 18F-FDG PET/CT scans in 20 multivisceral transplant recipients in whom previous non-functional imaging was deemed clinically inconclusive. The results were compared with histopathological and clinical follow-up data. In our study, the accuracy of 18F-FDG PET/CT was determined as 66.7%, where a final diagnosis was confirmed clinically or via pathology. Of the 28 scans, 24 scans (85.7%) directly affected patient management, of which 9 were related to starting of new treatments and 6 resulted in an ongoing treatment or planned surgery being stopped. This study demonstrates that 18F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy.

Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial.

PURPOSE: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. METHODS: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. RESULTS: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. CONCLUSION: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. TRIAL REGISTRATION: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063.

Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management.

OBJECTIVE: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period. DESIGN: Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed. RESULTS: Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden. CONCLUSION: Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease.

Optimization of PET/CT image quality using the GE 'Sharp IR' point-spread function reconstruction algorithm.

OBJECTIVE: The objective of this study was to quantify any improvement with the GE 'Sharp IR' point-spread function (PSF) reconstruction algorithm in addition to ordered subsets expectation maximum (OSEM) and time-of-flight (TOF) reconstruction algorithms and establish the optimum parameters to be used in clinical studies. MATERIALS AND METHODS: We conducted a range of experiments using the National Electrical Manufacturers Association image quality phantom filled with a 4 : 1 signal-to-background ratio. We scanned the phantom using the GE Discovery 690 PET/CT scanner. We varied iteration number and Gaussian filtration. Results were compared for OSEM, OSEM+TOF and OSEM+TOF+PSF reconstructions. A sample of 15 whole-body fluorine-18-fluorodeoxyglucose were reconstructed with OSEM+TOF and OSEM+TOF+PSF using a selection of optimum reconstruction parameters determined in phantom studies. Clinicians qualitatively ranked their preferred images to choose optimum parameters. RESULTS: The addition of PSF improved signal-to-noise ratios (SNRs), contrast, hot contrast recovery coefficients and noise over OSEM and OSEM+TOF reconstruction algorithms. SNRs were the highest at two iterations and with 0 or 2 mm filters with OSEM+TOF+PSF reconstruction in all phantom studies. Clinicians generally favoured OSEM+TOF+PSF reconstruction with three iterations and a 2 mm filter. CONCLUSION: PSF reconstruction significantly improved image quality for both clinical and phantom studies. We recommended the optimum reconstruction parameters using three iterations, 24 subsets and a 2 mm filter, which improved SNRs by up to 28.8% for small lesions (P<0.05).

Improved long-term survival after resection of colorectal liver metastases following staging with FDG positron emission tomography.

BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.

Does P-glycoprotein have a role in the lung clearances of inhaled 99mTc-sestamibi and 99mTc-tetrofosmin?

OBJECTIVE: The clearance rate of inhaled 99mTc-sestamibi from the lungs of healthy nonsmoking individuals is much slower than would be expected from its physical properties. The clearance rate is even slower in healthy cigarette smokers. As 99mTc-sestamibi is a substrate for P-glycoprotein (P-gp), pulmonary P-gp may be influential in 99mTc-sestamibi clearance and may be upregulated in smokers. 99mTc-tetrofosmin is also a substrate for P-gp, therefore we hypothesized that it would display similar kinetics to 99mTc-sestamibi and support a role for P-gp. We also hypothesized that administration of P-gp modulators would accelerate clearance of 99mTc-sestamibi. METHODS: We measured clearance rates of 99mTc-tetrofosmin in four healthy smokers and four healthy nonsmokers and of 99mTc-sestamibi in six otherwise healthy patients with psoriasis before and after 2 weeks of therapy with cyclosporine A (2.5-5 mg/kg/day) and two healthy women taking the oral contraceptive pill, as both cyclosporine and steroids are known to be P-gp modulators. RESULTS: The clearance rate of 99mTc-tetrofosmin in nonsmokers ranged from 0.38 to 0.63%/min, similar to the previously recorded rate for 99mTc-sestamibi [0.43 (SD 0.083)%/min], but it was not delayed in smokers (range 0.42-0.97%/min). Cyclosporine had no significant effect on 99mTc-sestamibi clearance, although clearance rates in the two women taking the oral contraceptive pill were both fast (0.58 and 0.62%/min). CONCLUSION: Although the role of P-gp expression in the clearance of 99mTc-sestamibi remains unproven, we conclude that 99mTc-tetrofosmin is not as P-gp-avid as 99mTc-sestamibi. A role for P-gp expression in the clearance of 99mTc-sestamibi remains unproven. Higher doses of P-gp inhibitors will be required and clearance rates correlated with immunohistochemical expression of P-gp.

Quality of CT pulmonary angiography for suspected pulmonary embolus in pregnancy.

The main objective of this study was to assess the quality of CT pulmonary angiography (CTPA) for suspected pulmonary embolus (PE) in the pregnant population. We retrospectively identified 40 consecutive pregnant patients who underwent CTPA from January 2005 to December 2006. Forty consecutive age-matched non-pregnant women were used as a control group. Studies were subjectively graded according to overall image quality by two readers in consensus, in randomised and blinded manner. Moreover, contrast enhancement of pulmonary arteries was subjectively and objectively evaluated. The proportion of sub-optimal studies was more than three times higher in the pregnant group (27.5%, n = 11) compared with the non-pregnant group (7.5%, n = 3; p = 0.015). Mean contrast enhancement was consistently higher in the non-pregnant group compared with pregnant group, both subjectively and objectively. The percentage of inadequately opacified vascular segments was more than two times higher in the pregnant group (28.7%, n = 264) than in the non-pregnant group (13.3%, n = 122; p = 0.0001). The incidence of sub-optimal CTPA studies is higher in pregnancy when compared with an age-matched non-pregnant control group. In addition to radiation issues, this should also be considered when implementing diagnostic strategies for suspected PE in pregnancy.

The role of bone scan in the diagnosis of carpal fracture in children.

A retrospective study was performed to evaluate the role of bone scan in the management of wrist trauma in children with equivocal radiographic findings. Thirty-one out of the 50 children showed no fracture. Six of them were treated for a median period of 9 days on clinical grounds; the others were discharged with reassurance. Four patients with evidence of soft tissue injury received no further treatment. Six of the 12 patients with a fracture on bone scan were treated with a cast for more than 4 weeks. None of the patients developed any complications. Bone scan is helpful when the diagnosis of a carpal fracture in children is equivocal.

Pulmonary elimination rate of inhaled 99mTc-sestamibi radioaerosol is delayed in healthy cigarette smokers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Very little is known about the physiology of P-glycoprotein (P-gp) expression in the lungs. * Ex vivo evidence based on resected lung tissue suggests that pulmonary P-gp is upregulated by cigarette smoke, but there are no in vivo studies to date. WHAT THIS STUDY ADDS: * The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled (99m)Tc-sestamibi, a P-gp substrate, provides for the first time a potential method for quantifying functional pulmonary P-gp expression that may inform about drug therapy by inhalation as well as provide a non-invasive, quantitative, human biomarker for assessing P-gp modulators. AIM: To explore inhaled technetium-99m-labelled hexakis-methoxy-isobutyl isonitrile ((99m)Tc-sestamibi) for quantifying pulmonary P-glycoprotein (P-gp) expression. METHODS: The elimination rate from the lungs of (99m)Tc-sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease. RESULTS: (99m)Tc-sestamibi elimination rates [% min(-1) (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated. CONCLUSION: Cigarette smoke upregulates lung P-gp. (99m)Tc-sestamibi elimination in normal smokers could be used to test new P-gp modulators. The findings also have implications for inhaled drug delivery.

Healthy passive cigarette smokers have increased pulmonary alveolar permeability.

QUESTION: Does passive smoking have a measurable effect on lung function in otherwise healthy subjects? There is current interest concerning passive smoking but no objective evidence showing that it has any impact on lung function. METHODS: The pulmonary clearance rate of (99m)Tc-DTPA was measured in 21 healthy volunteers after inhalation as a radio-aerosol and compared between healthy cigarette smokers, passive smokers and non-smokers. All volunteers had normal lung function. RESULTS: Clearance half-times in healthy passive smokers (n=5) were longer than in healthy smokers (n=6) but clearly shorter compared with healthy non-smokers (n=10) with respective mean values of 45.2 (SD 8.3), 24.3 (8.6) and 80.3 (20) min. CONCLUSION: Passive smoking has a functional impact on the lung blood/gas barrier.

Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient.

Current imaging guidelines recommend that many cancer patients undergo soft-tissue staging by computed tomography (CT) whilst the bones are imaged by skeletal scintigraphy (bone scan). New CT technology has now made it feasible, for the first time, to perform a detailed whole-body skeletal CT. This advancement could save patients from having to undergo duplicate investigations. Forty-three patients with known malignancy were investigated for bone metastasis using skeletal scintigraphy and 16-detector multislice CT. Both studies were performed within six weeks of each other. Whole-body images were taken 4 h after injection of 500 Mbq (99m)Tc-MDP using a gamma camera. CT was performed on a 16-detector multislice CT machine from the vertex to the knee. The examinations were reported independently and discordant results were compared at follow-up. Statistical equivalence between the two techniques was tested using the Newcombe-Wilson method within the pre-specified equivalence limits of +/-20%. Scintigraphy detected bone metastases in 14/43 and CT in 13/43 patients. There were seven discordances; four cases were positive on scintigraphy, but negative on CT; three cases were positive on CT and negative on scintigraphy. There was equivalence between scintigraphy and CT in detecting bone metastases within +/-19% equivalence limits. Patients who have undergone full whole-body staging on 16-detector CT may not need additional skeletal scintigraphy. This should shorten the cancer patient's diagnostic pathway.

Quantification of disease activity in patients undergoing leucocyte scintigraphy for suspected inflammatory bowel disease.

PURPOSE: Whole-body gamma camera counting is an alternative to faecal 111In collection for quantifying disease activity in inflammatory bowel disease (IBD) but requires administration of imaging activities of 111In. The aim of this study was to explore a dedicated whole-body counter which requires 20-fold less activity than gamma camera counting. METHODS: Thirty patients with known or suspected IBD received 99mTc-granulocytes (approximately 200 MBq) and 111In-granulocytes (approximately 0.5 MBq). The 99mTc-cells were injected 45 min after the 111In-cells and immediately after a baseline 111In whole-body count. The decay-corrected count at 120 h was expressed as a fraction of baseline to give whole-body 111In retention (WBR). One patient was excluded as the injected cells were non-viable. RESULTS: Median 45-min intravascular 111In recovery was 35% in patients compared with 43% in six normal volunteers (p<0.05). WBR in normals ranged from 91% to 93% and in 11 patients with negative 99mTc imaging from 87% to 96%. Only one of 11 patients with negative imaging had WBR <90% while 11/12 patients with WBR <90% had abnormal imaging. Ten of 13 patients with Crohn's disease (CD) had abnormal imaging. The lowest WBR in these ten was 77% and six had values of >90%. There was a significant association between WBR and 99mTc image grade (Rs=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (Rs=0.54, p>0.05). CONCLUSION: Dedicated whole-body counting is able to quantify disease activity in IBD but may give normal values in active CD.

Extensive skeletal muscle uptake of 18F-FDG: relation to immunosuppressants?

A case of gross skeletal muscle uptake of 18F-FDG during PET is described. The clinical context of immunosuppression after heart and lung transplantation and the absence of any other known association make the former a likely etiologic factor.

16-Detector multislice CT-skeletal scintigraphy image co-registration.

OBJECTIVE: Co-registration of bone scintigrams with radiographs has been used in the diagnosis of wrist injuries, although co-registration of tomographic bone scintigraphy with computed tomography (CT) has not been widely reported. We describe a co-registration technique in patients with possible wrist fracture. METHODS: The technique was used on three patients and involved placing the wrist on a Perspex board and tracing the outline of the forearm and hand with a pen to try and ensure accurate repositioning on the board for the two sets of imaging. Four point source markers were attached to the board during both examinations. Single photon emission computed tomography (SPECT) was performed 4 h after injection Tc-methylenediphosphonate (MDP), using a dual-headed gamma camera. CT images were acquired on a 16-detector CT unit. The SPECT and CT images were co-registered with commercially available image fusion software. The centre of the four markers was identified in both sets of images and a rigid body point match algorithm was used. Before patient studies, the technique was tested using a phantom. RESULTS: In all the phantom and clinical studies it was possible to identify the positions of all the markers. There were varying degrees of success in patient repositioning. CONCLUSION: We describe a technique that may aid the fusion of functional images from skeletal scintigraphy with the exquisite anatomical detail from the latest CT technology, in the detection of occult wrist fractures. The technique may aid fracture localization and/or detection and might help distinguish the clinically important scaphoid fractures from other benign carpal lesions.