Ian Cullum

Fusion of Metabolic Function and Morphology: Sequential [18F]Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Studies Yield New Insights Into the Natural History of Bone Metastases in Breast Cancer

PURPOSE By monitoring bone metastases with sequential [(18)F]fluorodeoxyglucose positron-emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging, this study investigates the clinical relevance of [(18)F]FDG uptake features of bone metastases with various radiographic appearances. PATIENTS AND METHODS Bone metastases were found in 67 of 408 consecutive patients with known/suspected recurrent breast cancer on [(18)F]FDG-PET/CT, characterized by CT morphology changes and/or bony [(18)F]FDG uptake. Twenty-five of the patients had sequential [(18)F]FDG-PET/CT examinations (86 studies) over an average follow-up period of 23 months. The temporal changes in [(18)F]FDG uptake and corresponding CT morphology features of 146 bone lesions identified in these 25 patients were followed up and correlated with therapeutic outcome retrospectively. RESULTS The 146 lesions were classified as osteolytic (77), osteoblastic (41), mixed-pattern (11), or no change/negative (17) on CT. The majority of the osteolytic (72; 93.5%) and mixed-pattern lesions (nine; 81.8%), but fewer of the osteoblastic lesions (25; 61%), showed increased [(18)F]FDG uptake. After treatment, 58 osteolytic lesions (80.5%) became [(18)F]FDG negative and osteoblastic on CT and only 14 relatively large lesions (19.5%) remained [(18)F]FDG avid. Of the 25 [(18)F]FDG-avid osteoblastic lesions, 13 (52%) became [(18)F]FDG negative, but 12 (48%) remained [(18)F]FDG avid and increased in size on CT. Five of the mixed-pattern lesions remained [(18)F]FDG avid after treatment. All 17 CT-negative lesions became [(18)F]FDG negative; however, nine of them became osteoblastic. None of the initially [(18)F]FDG-negative lesions showed [(18)F]FDG avidity during follow-up. CONCLUSION [(18)F]FDG uptake reflects the immediate tumor activity of bone metastases, whereas the radiographic morphology changes vary greatly with time among patients.

The in vivo distribution of 99Tcm-HM-PAO in normal man

The distribution of 99Tcm-HM-PAO is described in normal man. Since our initial report on the clinical potential of this new radiopharmaceutical in 1984, a number of clinical trials are in progress worldwide. As the tracer has been designed to enable the in vivo assessment of the distribution of cerebral blood flow in man, significant interest in this new 99Tcm-labelled compound can be detected not only in the nuclear medicine practice in general, but in the more specialist areas of medicine such as neurology and psychiatry. In this paper we report findings which should aid in the evaluation of this compound in normal individuals.

Vascular Inflammation Imaging with 18F-FDG PET/CT: When to Image?

We prospectively investigated the ideal imaging time to measure vascular uptake after injection of 18F-FDG. Methods: A total of 17 patients with atherosclerotic abdominal aortic aneurysm underwent dynamic abdominal PET/CT using 2-min frames between 45 and 53, 57 and 65, 115 and 123, and 175 and 183 min after injection of 18F-FDG. For each period of dynamic imaging, vessel wall and lumen uptake were measured using the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Results: No significant difference in TBR across all time points (repeated measures ANOVA, P = 0.206) was observed, despite a significant difference in aortic wall and lumen uptake with time (repeated measures ANOVA, P = 0.02 and P < 0.001, respectively). There was no significant difference between aortic wall uptake at 60 min (SUVmax, 2.15 ± 0.11 SE) and 180 min (SUVmax, 1.99 ± 0.18 SE) (paired t test, P = 0.367). There was a significant difference in lumen uptake at 60 min (SUVmax, 2.4 ± 0.11 SE) and 180 min (SUVmax, 1.7 ± 0.1 SE) (paired t test, P = 0.001). There was no significant difference in TBR between 60 min (0.91 ± 0.03) and 180 min (1.01 ± 0.06 SE) (paired t test, P = 0.131). With increasing delayed imaging, there was increasing variability (SE) in the SUVmax for the aortic wall and TBRs. Conclusion: There was no significant advantage in imaging at 3 h over 1 h after 18F-FDG injection.

Clinical outcome after one year following samarium-153 particulate hydroxyapatite radiation synovectomy.

The clinical outcome and tolerability following treatment with samarium-153 particulate hydroxyapatite was evaluated in patients with persistent rheumatoid knee synovitis. The clinical review of 18 patients treated with intra-articular samarium-153 particulate hydroxyapatite combined with triamcinolone hexacetonide who had failed to obtain more than 4 weeks symptom relief from a prior intra-articular glucocorticoid injection was undertaken. No unwanted effects from the treatment were observed. Symptom relief was maintained in 56% patients at 6 months and in 44% of patients at 12 months following treatment. Median duration of symptom relief was 9 months. There was a significantly higher mean baseline Ritchie Articular Index in patients relapsing within 3 months and a trend towards earlier relapse in patients with higher indices of disease activity at the time of treatment. There was a trend towards earlier relapse in patients with a poor range of knee flexion at baseline and with worse indices of intra-articular radiopharmaceutical distribution. Samarium-153 particulate hydroxyapatite knee synovectomy is well tolerated and may be an effective treatment for carefully selected patients with persistent rheumatoid knee synovitis.

Low-statistics reconstruction with AB-EMML

In dynamic SPECT studies with short acquisition times per time-frame, data with very low-statistics is obtained. For such cases standard iterative reconstruction algorithms based on multiplicative correction factors, automatically including a non-negativity constraint, might not be Ideal. The AB-EMML algorithm allows the user to include prior information on the upper and lower bounds for the image values. We have used this algorithm with a negative lower bound for reconstruction of low-statistics SPECT data in order to allow for negative image values. Our results show that this method can preserve quantitative accuracy at low count levels, where standard methods produces biased values. Furthermore, the noise is much more uniformly distributed-lower in high intensity regions and higher in low intensity regions. The convergence is generally slower, but faster in cold regions.

Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

Abstract The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.

How often do patients undergo repeat PET or PET/CT examinations? Experience from a UK institution.

Background and aimAccording to the report of the Intercollegiate Standing Committee on Nuclear Medicine, the UK requires 40–60 positron emission tomography (PET) machines in the next decade (Intercollegiate Standing Committee on Nuclear Medicine). Positron Emission Tomography: a Strategy for Provision in the UK. London: Royal College of Physicians of London; 2003, pp. 1–9). This figure is based mainly on patients receiving only one examination and restricting the clinical indication to three primary diagnoses. The aim of this study was to assess the appropriateness of this figure and the assumptions made in the Intercollegiate report on UK PET provision. MethodsWe examined retrospectively our institutions entire PET and PET/computed tomography (CT) database, which spans 4 years and 9 months. We recorded the number of patients who received repeat examinations. ResultsReports were available for 3354 PET/CT or PET-only studies; 418 of 2268 patients (18.4%) received at least one repeat PET/CT examination. The three main indications for PET examination in the Intercollegiate report only accounted for approximately 60% of the examinations undertaken. ConclusionOur records suggest that basing the UKs future PET provision on a single examination and on three clinical indications only is no longer realistic.

In vivo imaging reveals increased eosinophil uptake in the lungs of obese asthmatic patients.

Using radiolabeled eosinophils coupled with SPECT/CT the authors quantify eosinophilic inflammation in the lungs of patients with asthma and focal pulmonary eosinophilic inflammation, revealing important differences in eosinophil kinetics between obese and non-obese asthmatics.

S65 Quantification of ‘whole lung’ pulmonary eosinophilic inflammation using radiolabelled autologous human eosinophils

Background Eosinophils are key mediators of allergic inflammation. The ability to localise and quantify eosinophilic inflammation in vivo would facilitate patient endotyping and evaluation of eosinophil-targeted therapeutics. We aimed to quantify eosinophil distribution and organ-specific uptake in healthy subjects, asthmatics, and patients with focal pulmonary eosinophilic inflammation. Methods We injected autologous radiolabelled eosinophils into 8 healthy volunteers, 15 asthmatics (7 obese and 7 non-obese), and 3 patients with focal eosinophilic inflammation and monitored eosinophil distribution (planar imaging, single photon emission computed tomography – SPECT)/CT). Lung accumulation of technetium-99 m-labelled eosinophils was quantified (Patlak-Rutland analysis). Whole body indium-111-labelled eosinophil distribution and loss were further assessed in 5 healthy volunteers and 7 asthmatics using a whole body counter. Findings Pulmonary eosinophil clearance was increased in patients with focal eosinophilia (0·0033 ml/min/ml; 95% CI −0·005–0·011; p=0.02) compared to asthmatics (0·0007 ml/min/ml; 95% CI 0·0003–0·0010; p=0.14) and controls (0·0003 ml/min/ml; 95% CI −7·5 × 10–5–0·0008). Absolute lung eosinophil migration was elevated in patients with focal inflammation (5932 eosinophils/min/ml; 95% CI −14351–26215, p=0.01) and asthma (364 eosinophils/min/ml; 95% CI 38–689; p=0.03) versus healthy volunteers (38 eosinophils/min/ml; 95% CI −11–87). Stratification of asthmatics based on BMI revealed increased pulmonary eosinophil clearance in obese (0·001 ml/min/ml; 95% CI 0·0007–0·001; p=0.02) versus non-obese asthmatics (0·0003 ml/min/ml; 95% CI −0·0002–0·0009). Interpretation Eosinophil radiolabelling can quantify pulmonary eosinophilic inflammation, with the potential for patient endotyping and testing eosinophil-targeted treatments. Funding Medical Research Council, Wellcome Trust, Asthma UK, Cambridge NIHR Biomedical Research Centre.

Attenuation map reconstruction from emission and transmission SPECT data

Attenuation correction is an essential step in single photon emission computed tomography (SPECT) reconstruction, and the required attenuation map can be determined from a transmission scan. The major drawback of this procedure is limited count statistics, due to time and dose considerations. It is well known that emission data also contains information about the attenuation distribution. In order to utilize this information, we have developed an attenuation map reconstruction method, which incorporates both emission and transmission data. The method is based on an existing transmission ML-EM algorithm, and the aim is to improve the photon statistics and reduce the noise in the final image. The method was evaluated using simulated data, and the results show that this new method can result in attenuation maps with a lower noise level and a more uniform noise distribution, as compared to using transmission data only.