Wolfgang Eschner

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Smoking upregulates α4β2* nicotinic acetylcholine receptors in the human brain

Abstract The role of the α4β2* nicotinic acetylcholine receptors (nAChR) in tobacco addiction in humans is largely unresolved. We visualized brain α4β2* nicotinic acetylcholine receptors of smokers and non-smokers with positron emission tomography using 2-[ 18 F]fluoro-3-(2( S )azetidinylmethoxy)pyridine, commonly known as 2-[ 18 F]F-A-85380. The total brain distribution volume of 2-[ 18 F]F-A-85380 was significantly increased in smokers. Statistical parametric mapping revealed that the most prominent regional differences of distribution volumes (DV) were found in cerebellum and brainstem with an increased uptake in smokers. The up-regulation of α4β2* nAChR upon chronic nicotine exposure via tobacco smoking incorporates subcortical brain regions which may play an important role in nicotine addiction.

Imaging of central nervous system lymphomas with iodine‐123 labeled rituximab

Most patients with primary central nervous system (CNS) lymphoma (PCNSL) relapse after initial response to chemotherapy or the combination of chemotherapy and irradiation. Thus, novel treatment regimens for relapsed PCNSL are needed. As the majority of PCNSL are B‐cell neoplasms expressing the CD20 antigen, treatment with the chimeric monoclonal antibody (MAb) rituximab might be reasonable. Nevertheless, the potential efficacy of intravenous rituximab in PCNSL seems to be limited as MAbs are high molecular weight proteins, which might be unable to pass the blood brain barrier. Thus, we performed dosimetric measurements with iodine‐123 (123I)‐rituximab to evaluate rituximab uptake in PCNSL after systemic intravenous administration. We analyzed four patients with PCNSL receiving a preinfusion of 250 mg/m2 rituximab followed by 200–500 MBq of the gamma‐emitter 123I‐rituximab. Single photon emission computed tomography (SPECT) was performed 1, 24 and 48 h after administration of the radio‐immunoconstruct. Only one patient showed a very weak or questionable uptake of 123I‐rituximab into tumor tissue which was ninefold lower compared with the blood‐pool accumulation. These data suggest that systemic MAb‐based radio‐immunotherapy is not feasible in patients with PCNSL because a sufficient activity in the tumor will be associated with severe hematotoxicity. If an uptake of therapeutic rituximab doses into PCNSL can be achieved remains questionable.

EANM Dosimetry Committee Series on Standard Operational Procedures for Pre-Therapeutic Dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases

The EANM Dosimetry Committee Series “Standard Operational Procedures for Pre-Therapeutic Dosimetry” (SOP) provides advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This particular SOP describes how to tailor the therapeutic activity to be administered for radioiodine therapy of benign thyroid diseases such as Graves’ disease or hyperthyroidism. Pretherapeutic dosimetry is based on the assessment of the individual 131I kinetics in the target tissue after the administration of a tracer activity. The present SOP makes proposals on the equipment to be used and guides the user through the measurements. Time schedules for the measurement of the fractional 131I uptake in the diseased tissue are recommended and it is shown how to calculate from these datasets the therapeutic activity necessary to administer a predefined target dose in the subsequent therapy. Potential sources of error are pointed out and the inherent uncertainties of the procedures depending on the number of measurements are discussed. The theoretical background and the derivation of the listed equations from compartment models of the iodine kinetics are explained in a supplementary file published online only.

Downregulation of 18F-FDG Uptake in PET as an Early Pharmacodynamic Effect in Treatment of Non–Small Cell Lung Cancer with the mTOR Inhibitor Everolimus

Everolimus downregulates glucose metabolism–associated genes in preclinical models. Inhibition of glucose metabolism measured by 18F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non–small cell lung cancer (NSCLC) patients. Methods: In 8 NSCLC patients treated with everolimus, the percentage change in 18F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a variety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and body weight and with and without correcting for plasma glucose levels. Results: In 5 patients, a reduction of 18F-FDG PET uptake on day 8 was observed with all methods, ranging from −12.8% to −72.2%. Conclusion: These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using 18F-FDG PET.

Iterative reconstruction: an improvement of technetium-99m MIBI SPET for the detection of parathyroid adenomas?

Abstract.The purpose of this study was to assess the value of technetium-99m methoxyisobutylisonitrile (MIBI) single-photon emission tomography (SPET) and an iterative reconstruction algorithm for the preoperative localisation of parathyroid adenomas (PTAs). Seventy-two patients (26 male, 46 female, mean age 58±16 years) with known primary hyperparathyroidism were examined preoperatively. First, a thyroid examination was performed to detect possible MIBI-accumulating thyroid lesions. Planar scans were then acquired 15 and 120 min and tomographic images 120 min after intravenous injection of 740 MBq 99mTc-MIBI, using a triple-head gamma camera (Picker Prism 3000). Additionally, 99mTc-MIBI/ 99mTc-pertechnetate subtraction scintigraphy of the early planar images was performed. The SPET data were evaluated using an iterative reconstruction (multiplicative iterative SPET reconstruction: MISR) as well as a standard algorithm (FBP: filtered back-projection with application of a 3-D low-pass postfilter). The weight of the resected PTAs ranged from 110 mg to 5 g. Using planar MIBI scans, correct localisation of the side of the PTA was possible in 81% of cases (58% for PTAs weighing less than 500 mg). Sensitivity increased to 94% using SPET and FBP, while with MISR it rose further, to 97%. Patients with PTAs weighing less than 500 mg showed a sensitivity of 88% with MISR and 81% with FBP. Furthermore, there was a clear improvement in image quality using MISR. None of the normal parathyroid glands were visualised. This study indicates that, in comparison with planar scintigraphy, 99mTc-MIBI SPET is a more sensitive and specific tool for topographical localisation of PTAs, especially those that are small. There is a further improvement in sensitivity and image quality when iterative reconstruction is used instead of FBP.

Bildrekonstruktion und Quantifizierung in der Emissionstomographie

Radionuclide tomographic imaging has substantially benefited from the introduction of statistical image reconstruction. Although the main concepts of these iterative algorithms were published decades ago, their widespread use in clinical routine only became available with faster computers for image processing in the last few years. This article gives an overview of data acquisition and iterative reconstruction in emission tomography, deals with the popular maximum likelihood algorithm, and describes the basics of the maximum a posteriori reconstruction. Prerequisites and corrections necessary for quantification are discussed in the second part of the article on the basis of positron emission tomography. Improvements in technical equipment are expected to stimulate future research into image reconstruction.Radionuclide tomographic imaging has substantially benefited from the introduction of statistical image reconstruction. Although the main concepts of these iterative algorithms were published decades ago, their widespread use in clinical routine only became available with faster computers for image processing in the last few years. This article gives an overview of data acquisition and iterative reconstruction in emission tomography, deals with the popular maximum likelihood algorithm, and describes the basics of the maximum a posteriori reconstruction. Prerequisites and corrections necessary for quantification are discussed in the second part of the article on the basis of positron emission tomography. Improvements in technical equipment are expected to stimulate future research into image reconstruction.

Recombinant Human TSH Increases Uptake and Effective Half-life of Radioiodine in Thyroid Hormone Secreting Metastases of Follicular Thyroid Cancer

Follicular thyroid cancer with thyroid hormone secreting metastases is an extremely rare condition, with only a few cases reported world-wide. We here present the case of a 64-year-old female patient affected by follicular thyroid cancer with extensive thyroid hormone secreting metastases leading to TSH-suppression. We have also summarized the relevant diagnostic and therapeutic approaches and describe, for the first time, the effects of rhTSH-application in this rare tumor entity. In this patient, we found that rhTSH increased ¹³¹I-uptake into the thyroid hormone secreting metastases and prolonged the effective half-life of ¹³¹I. These effects of rhTSH should be considered when fixed activities of ¹³¹I are prescribed.

Kalibration eines Ganzkörperzählers mit Monte-Carlo-Methoden

Zusammenfassung Mit Ganzkorperzahlern konnen radioaktive Stoffe im menschlichen Korper gammaspektrometrisch identifiziert und quantifiziert werden. Durch Messungen mit Phantomen, die das Schwachungsverhalten des menschlichen Korpers fur Strahlung nachbilden, werden die zur Berechnung der inkorporierten Aktivitat benotigten Effizienzfaktoren fur ausgewahlte Nuklide gewonnen. Fur den Kolner Ganzkorperzahler wurde die Spektrometrie in Monte-Carlo-Rechnungen mit dem EGSnrc-System simuliert. Die mit Flaschenphantomen gemessenen Spektren konnten qualitativ und quantitativ durch die Simulationen nachvollzogen werden (z. B. fur K-40 mit einer Genauigkeit von ± 2%). Fur simulierte Verschiebungen des Phantoms langs der Liege ergab sich jeweils ein parabelformiger Verlauf mit Anderungen der Effizienzen von bis zu 5 %. Durch gewichtete Summation von Effizienzen, die sich aus der Simulation fiktiver monoenergetischer Nuklide ergeben, konnen auch Nuklide quantifiziert werden, fur die keine Phantommessungen moglich sind. Simulationen mit einem einfachen Menschenmodell zeigten fur I-131 eine deutliche Abhangigkeit der Effizienz von der Verteilung des Radionuklids im Korper, die in der Auswertung der Spektren berucksichtigt werden muss. In den Simulationen ist der Einfluss des Skelettes auf die Effizienzen hingegen gering. Bei gleicher Masse fallt die Effizienz linear mit der Korperlange um bis zu 6 % ab. Dieses muss bei Messungen, in denen eine hohe Genauigkeit erforderlich ist, berucksichtigt werden. Fur die Anforderungen im Routinebetrieb als Inkorporationsmessstelle sind die in der Flaschengeometrie durch Phantommessungen oder Simulationen bestimmten Effizienzfaktoren ausreichend.

[Established nuclear medicine techniques for tumour diagnosis (tumour SPECT): can they still compete with (18)F-FDG-PET?].

This overview presents the indications of tumour SPECT in contrast to tumour PET using (18)F-FDG. A number of diagnostic SPECT radiopharmaceuticals have been used for years in oncology and are widely available in nuclear medicine departments. Today, tumour SPECT has to compete with tumour PET using (18)F-FDG. Other PET radiopharmaceuticals are common only in specialised centers. In comparison to SPECT, PET images with their higher resolution are technically superior. Therefore, PET is better than SPECT in localising a tumour, if the special tumour entity accumulates (18)F-FDG. Thus, (18)F-FDG-PET has largely replaced SPECT examinations using (201)Tl chloride, (67)Ga citrate or (99m)Tc anti-CEA. It is questionable whether mammascintigraphy using (99m)Tc-MIBI or (99m)Tctetrofosmine will be broadly accepted in clinical routine. SPECT radiopharmaceuticals are still up to date for examination of tumour entities which do not accumulate (18)F-FDG (e. g. neuroendocrine tumours) and in clinical problem solving if (18)F-FDG-PET is not regarded as superior (e. g. search for recurrent medullary thyroid carcinoma) or in the management of tumours with overlapping diagnosis and therapy as it is the case for differentiated thyroid carcinomas ((123)I/(131)I-NaI), phaeochromozytomas, and neuroblastomas ((123)I/(131)I-MIBG), carcinoids, gastroenteropancreatic tumours, paragangliomas, and Merkel-cell tumours (somatostatin receptor scintigraphy). Future developments concerning new SPECT radiopharmaceuticals and image fusion such as SPECT/CT are expected.