Pál Mikecz

Attenuation correction in PET using consistency information

In this study the authors use the consistency conditions of the Radon transform to aid attenuation correction in PET. The conditions are used both for estimating the parameters of a uniform elliptical attenuation distribution (without any transmission measurements) and for correcting for patient motion between the transmission and emission acquisitions. The results show that, for a uniform elliptical attenuation distribution, the reconstructed count densities obtained using attenuation correction based on the consistency conditions are within 1% of the true values. The method is shown to be fairly tolerant to the effects of photon counting statistics and to small non-uniformities in the attenuation distribution (such as skull attenuation). The results also show that the consistency conditions may be useful in correcting for patient motion. The method is shown to effectively compensate for shifts in two dimensions using both simulated and experimental data.

Prevalence of hibernating myocardium in patients with severely impaired ischaemic left ventricles

Objective Severe impairment of left ventricular (LV) contraction is associated with an adverse prognosis in patients with ischaemic heart disease. Revascularisation may improve the impaired LV contraction if hibernating myocardium is present. The proportion of patients likely to benefit from this intervention is unknown. Therefore, the prevalence of hibernating myocardium in patients with ischaemic heart disease and severe impairment of LV contraction was assessed. Design From a consecutive series of patients undergoing coronary angiography for the investigation of chest pain or LV impairment, all patients with ischaemic heart disease and an LV ejection fraction (LVEF) ⩽ 30% were identified. These patients underwent positron emission tomography (PET) to detect hibernating myocardium, identified by perfusion metabolism mismatch. Setting A teaching hospital directly serving 500 000 people. Results Of a total of 301 patients, 36 had ischaemic heart disease and an LVEF ⩽ 30%. Twenty-seven patients had PET images, while nine patients were not imaged because of emergency revascularisation (three), loss to follow up (one), inability to give consent (four), and age < 50 years (one, ethics committee guidelines). Imaged and non-imaged groups were similar in LV impairment, demographic characteristics, and risk factor profile. Fourteen patients (52% of the imaged or 39% of all patients with ischaemic heart disease and LVEF ⩽ 30%) had significant areas of hibernating myocardium on PET. Conclusion It is possible that up to 50% of patients with ischaemic heart disease and severely impaired left ventricles have hibernating myocardium.

[F18]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: Preliminary results from a prospective histology-based study

PURPOSE To evaluate the diagnostic potential of PET/CT using ([F(18)]fluorethylcholine (FEC) for lymph node (LN) staging in high risk prostate cancer (PCa) patients prior to radical prostatectomy (RP). PATIENTS AND METHODS Twenty patients with localised PCa and > or =20% LN risk according to a published nomogram were prospectively enrolled. FEC PET/CT was done minimum 14 d after prostate biopsy. Afterwards, open RP and extended pelvic LN dissection (ePLND) were performed. Clinical stage, Prostate Specific Antigen (PSA) and biopsy Gleason Grading were assessed and histopathological evaluation of the RP-specimens and dissected LN has been performed. The results from PET/CT were compared with LN metastasis according to their anatomical site. RESULTS Overall, 285 LN have been removed with a mean number of 15 nodes per patient (7-26). Of the 20 patients, 9 men were LN positive (45%), which corresponds to 31 positive LN with a mean size of 7 mm (0.8-12 mm). Dissection of the obturator fossa, external iliac artery/vein and internal iliac artery/vein revealed 36%, 48% and 16% of positive LN, respectively. FEC PET/CT did not detect one single positive LN, thus was false-negative in 31 metastasis and true negative in 254 LN. CONCLUSION Based on our results which confirmed experience from the previous studies, FEC PET/CT scan did not prove to be useful for LN staging in localised PCa prior to treatment and should thus not be applied if clinically occult metastatic disease is suspected.

Excitation functions of (p, xn) reactions on natTi: Monitoring of bombarding proton beams

Abstract Excitation functions have been measured for the natTi(p, x)48V nuclear process by the stacked-foil technique in the energy range up to 30 MeV for use as a monitor reaction for proton beams. The intercomparison shows good agreement with other monitor reactions (p + natCu, p + natNi) over the whole energy range. Excitation functions for the production of 47Sc, 44mSc, 44gSc and 43Sc isotopes and the isomeric cross section ratio of 44mSc/44gSc were also determined in the energy range from 9.0 to 17.5 MeV.

Gene Expression Patterns and Tumor Uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an Orthotopic Mouse Xenotransplantation Model of Pancreatic Cancer

Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human pancreatic tumor cell lines after xenotransplantation into SCID mice and to correlate tumor uptake with gene expression of membrane transporters and rate-limiting enzymes for tracer uptake and tracer retention. Methods: Four weeks after orthotopic inoculation of human pancreatic carcinoma cells (PancTuI, Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small-animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to-liver uptake ratios (TLRs) of the tracers were compared with gene expression profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic tumor tissue based on gene microarray analysis and quantitative polymerase chain reaction. Results: 18F-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue. Relevant genes involved in the uptake of 18F-FEC were predominantly unaffected or downregulated in the tumor cell lines. Conclusion: In comparison to 18F-FDG and 18F-FEC, 18F-FLT was the PET tracer with the highest and most consistent uptake in various human pancreatic tumor cell lines in SCID mice. The imaging results could be explained by gene expression patterns of membrane transporters and enzymes for tracer uptake and retention as measured by gene array analysis and quantitative polymerase chain reaction in the respective cell lines. Thus, standard molecular techniques provided the basis to help explain model-specific tracer uptake patterns in xenotransplanted human tumor cell lines in mice as observed by PET.

Can the surface electrocardiogram be used to predict myocardial viability

OBJECTIVE To investigate whether QRS morphology on the surface ECG can be used to predict myocardial viability. DESIGN ECGs of 58 patients with left ventricular impairment undergoing positron emission tomography (PET) were studied. 13N-Ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) were the perfusion and the metabolic markers, respectively. The myocardium is scarred when the uptake of both markers is reduced (matched defect). Reduced NH3 uptake with persistent FDG uptake (mismatched defect) represents hibernating myocardium. First, the relation between pathological Q waves and myocardial scarring was investigated. Second, the significance of QR and QS complexes in predicting hibernating myocardium was determined. RESULTS As a marker of matched PET defects, Q waves were specific (79%) but not sensitive (41%), with a 77% positive predictive accuracy and a poor (43%) negative predictive accuracy. The mean size of the matched PET defect associated with Q waves was 20% of the left ventricle. This was not significantly different from the size of the matched PET defects associated with no Q waves (18%). Among the regions associated with Q waves on the ECG, there were 16 regions with QR pattern (group A) and 23 regions with QS pattern (group B). The incidence of mismatched PET defects was 19% of group A and 30% of group B (NS). CONCLUSIONS Q waves are specific but not sensitive markers of matched defects representing scarred myocardium. Q waves followed by R waves are not more likely to be associated with hibernating myocardium than QS complexes.

Incidence of hibernating myocardium after acute myocardial infarction treated with thrombolysis.

OBJECTIVE: To establish the incidence of hibernating myocardium after myocardial infarction treated with thrombolysis and to observe differences in the clinical outcome between patients with and without hibernating tissue. METHODS: 41 patients underwent gated positron emission tomography with 18-fluorodeoxyglucose and 13N-ammonia at a median of eight days after first myocardial infarction. RESULTS: All 41 subjects had a matched perfusion-metabolism deficit in the region of myocardium indicated as the site of infarction by an electrocardiograph; 32 patients (78%) had scans which also showed at least one area of reduced blood flow and contraction with a concomitant increase in glucose uptake, representing hibernating myocardium. Patients were followed up at a median of six months: all 41 were alive and none had sustained a further infarct or cardiac arrhythmia; 17 subjects with hibernating tissue (53.1%) and two without (25%) reported chest pain after myocardial infarction. CONCLUSIONS: Hibernating myocardium is relatively common shortly after myocardial infarction treated with thrombolysis. It does not influence mortality or the incidence of postinfarction chest pain.

Cross sections of proton induced nuclear reactions on enriched 111Cd and 112Cd for the production of 111In for use in nuclear medicine

Proton induced nuclear reactions on enriched 111Cd and 112Cd have been studied up to 30 MeV in the context of routine production of the medically used isotope 111In with low and medium energy cyclotrons. The excitation functions of 111Cd(p,n)111m,gIn and 112Cd(p,2n)111m,gIn as production reactions and 111Cd(p,2n)110mIn, 111Cd(p,2n)110In, 111Cd(p,3n)109ml,m2,In, 112Cd(p,3n)110mIn, 112Cd(p,3n)110gIn as competing processes have been measured using the activation method involving the stacked-foil technique. The deduced thick target yields are compared with those obtained experimentally.

Synthesis of 5'-N-(2-[18F]Fluoroethyl)-carboxamidoadenosine: A promising tracer for investigation of adenosine receptor system by PET technique

5′-N-(2-[18F]Fluoroethyl)-carboxamidoadenosine ([18F]FNECA), a promising 18F-labelled adenosine agonist has been prepared by two different synthetic routes. In the first, [18F]fluoride was reacted with 5′-N,N-ethylene-2,′,3′-O-isopropylidenecarboxamido-adenosine and after removing the protective group [18F]FNECA was obtained in a low radiochemical yield (1±1%, means±sd, n=7, decay corrected). In the second, 2-[18F]fluoro-ethylamine was synthesised according to the literature and reacted with 2′,3′-O-isopropylideneadenosine-5′-uronic acid in the presence of a coupling agent. The following hydrolysis step provided the [18F]FNECA with a modest radiochemical yield (24±9%, n=17, based on [18F]fluoride-activity). After purification by preparative reverse phase HPLC 18·9–166·5 MBq (0·51–4·5 mCi) [18F]FNECA was obtained with a specific activity of 2·35±1·14 TBq/mmol (63·5±30·9 Ci/mmol, n-3). The total synthesis took 200 min and the decay corrected radiochemical yield based on [18F]F− activity was 17±9% (n=5) with more than 99·9% radiochemical purity. This second route provides sufficient [18F]FNECA for the subsequent biological evaluation using PET-technique. Copyright

Pgp inhibition by UIC2 antibody can be followed in vitro by using tumor-diagnostic radiotracers, 99mTc-MIBI and 18FDG.

P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g. cyclosporine A and SDZ PSC 833) used at low concentrations and UIC2 antibody is a novel, specific, and effective way of blocking Pgp function (Goda et al., 2007). In the present work we study the UIC2 antibody mediated Pgp inhibition in more detail measuring the accumulation of tumor diagnostic radiotracers, 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), into Pgp(+) (A2780AD) and Pgp(-) (A2780) human ovarian carcinoma cells. Co-incubation of cells with UIC2 and cyclosporine A (CSA, 2μM) increased the binding of UIC2 more than 3-fold and reverted the rhodamine 123 (R123), daunorubicin (DNR) and (99m)Tc-MIBI accumulation of the Pgp(+) 2780AD cells to approx. the same level as observed in Pgp(-) cells. Similarly, 50μM paclitaxel (Pacl) increased UIC2 binding, and consequently reinstated the uptake of R123, DNR and (99m)Tc-MIBI into the Pgp(+) cells. Blocking Pgp by combined treatments with CSA+UIC2 or Pacl+UIC2 also decreased the glucose metabolic rate of the A2780AD Pgp(+) cells measured in (18)FDG accumulation experiments suggesting that the maintenance of Pgp activity requires a considerable amount of energy. Similar treatments of the A2780 Pgp(-) cells did not result in significant change in the R123, DNR, (99m)Tc-MIBI and (18)FDG accumulation demonstrating that the above effects are Pgp-specific. Thus, combined treatment with the UIC2 antibody and Pgp modulators can completely block the function of Pgp in human ovarian carcinoma cells and this effect can be followed in vitro by using tumor-diagnostic radiotracers, (99m)Tc-MIBI and (18)FDG.