Michael Andreeff

Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations

AIM Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOC- for patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. PATIENTS, METHODS Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112+/-22) MBq 68Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i.. Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). RESULTS Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. CONCLUSION 68Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose).

PET aerosol lung scintigraphy using Galligas

Dear Sir, The trend in imaging—no matter if in radiology or nuclear medicine—goes towards smaller voxels acquired in less time with less radiation dose. Thus, it is merely a matter of time or costs when conventional methods like bone, sentinel lymph node (SLN), octreotide or lung ventilation/ perfusion scans are replaced by PET/CT. The costs of PET/ CT can be dramatically reduced when using the generatorproduced positron emitter Ga instead of F, which requires a cyclotron. Regarding perfusion imaging, binding Ga to macroaggregated albumin or microspheres had already been proposed in 1979 [1] and is possibly experiencing its renaissance in the molybdenum—and consequently Tc—crisis [2] and/ or with the increasing use and spread of PET/CT scanners and Ga generators [3, 4]. However, for PET lung ventilation/perfusion imaging an analogue to Technegas [5, 6] is still missing. Therefore, we used Ga instead of Tc to produce a radioaerosol feasible for PET imaging. Ga (1,110 MBq) was eluted from a commercially available generator (1,110 MBq) (Eckert & Ziegler AG, Berlin, Germany) based on a titanium oxide phase adsorbing Ge(IV) equipped with a labelling module (ModularLab) providing an elution and cleaning programme. About 0.15 ml (150–200 MBq) of this solution was loaded into a graphite crucible (AlmediS Altmann GmbH, Salzgitter, Germany) and simmered in an atmosphere of pure argon using a commercially available Technegas generator (Tetley Manufacturing Ltd., Sydney, Australia). Following vaporization inhalation was performed in a common manner according to the manufacturer’s instructions. Two healthy male volunteers (age: 46 and 50 years) inhaled the radioaerosol, one in the prone position and the other in the supine position, and underwent PET/CT in an early and late phase (15 min and 3.5 h, respectively) after inhalation. PET imaging was performed on a 16-slice PET/CT (HIREZ biograph Sensation 16, Siemens/CTI, Knoxville, TN, USA) providing an axial field of view of 15.5 cm and an image resolution 4.5 mm in all three dimensions. The CT acquisition protocol included a low-dose CT (10 mAs, 120 kV, 0.5 s per rotation, 5-mm slice thickness) from the neck to mid-thigh for attenuation correction. PET scans were acquired in 3-D mode with an acquisition time of 3 min per bed position. Images were reconstructed by an iterative algorithm with attenuation and scatter correction (6 iterations, 4 subsets) followed by a post-reconstruction smoothing Gaussian filter (5 mm full-width at halfmaximum). The PET/CT system is calibrated with a Ge/Ga phantom (1.94 cps/kBq true coincidence). PET imaging demonstrated intense radiotracer uptake in the lungs without bronchial deposits (Fig. 1). Late images demonstrated persistent tracer distribution with only trace activity in the urinary bladder and a lack of radioactivity in the blood pool or abdomen (Fig. 2). Early PET imaging revealed 12 million ECAT counts in the 3-min bed position corresponding to an activity of 35 MBq. Late PET imaging J. Kotzerke (*) :M. Andreeff :G. Wunderlich Klinik und Poliklinik für Nuklearmedizin, Technische Universität Dresden, Dresden, Germany e-mail: joerg.kotzerke@mailbox.tu-dresden.de

Radiosynoviorthesis (RSO): influencing factors and therapy monitoring

ObjectiveTo evaluate the effectiveness of radiosynoviorthesis (RSO) in relation to joint type and underlying disease by both self-assessment of patients and scintigraphic assessment to determine conditions under which RSO might be preferable to the sole intra-articular corticoid injection.MethodsRadiosynoviorthesis was performed on 136 patients for 424 joints [242 small, 130 medium-sized, and 52 large joints; 313 with rheumatoid arthritis (RA) and 111 with osteoarthritis (OA)]. The success of RSO was evaluated after 12 months by patients’ estimation, and in 35 patients for 157 joints additionally by two-phase bone scintigraphy. The relative change in the scintigraphic uptake was compared with the patients’ estimation.ResultsThe subjectively estimated success rates for the small, medium-sized, and large joints were 89% (215/242), 86% (112/130), and 79% (41/52), and for RA and OA 89% (280/313) and 79% (88/111), respectively. The scintigraphically determined response rates for small and medium-sized joints were 81% (86/106) and 69% (35/51), respectively. There was a mismatch between patients’ assessment and scintigraphic assessments in 18% (28/157) with 6 false-negative and 22 false-positive estimations using scintigraphy as the standard of reference.ConclusionsThe success of RSO is higher in patients with RA than in patients with OA. For the finger, ankle, and wrist joints in RA, RSO is so promising that we would like to advocate its preference over the sole intraarticular corticoid injection. Perfusion bone scintigraphy can be used for therapy monitoring and earlier switching to RSO by showing that other therapies have failed.

Ventilation-perfusion-lungscintigraphy using PET and 68Ga-labeled radiopharmaceuticals

AIM Imaging of lung perfusion with positron emission tomography (PET) is already possible with 68Ga labeled denaturized albumin. The purpose of our study was to produce and test a 68Ga labeled aerosol (Galligas®) for ventilation and 68Ga labeled albumin particles (microspheres) for perfusion imaging with PET. PATIENTS, METHODS Galligas was produced by simmering and burning generator eluted 68Ga solution (100 MBq/0.1 ml) in an ordinary technegas generator. Fifteen patients with suspicion on pulmonary embolism underwent PET/CT (Biograph 16) after inhalation of Galligas and application of 68Ga labeled microspheres. A low dose CT was acquired for attenuation correction (AC). Images were reconstructed with and without AC. The inhaled activity was calculated compared to the activity injected. RESULTS Inhaled radioaerosol Galligas demonstrated typical distribution as known from 99mTc-labeled technegas with homogeneous distribution in lung without hilar deposits. Attenuation corrected images resulted in artefacts in the lung base. Therefore, non-corrected images were used for making the results. Three out of fifteen patients showed a deficient perfusion whereas ventilation was normal corresponding to pulmonary embolism. CONCLUSION Lung scintigraphy with PET is feasible. Galligas is simple to produce (analogously to technegas). 68Ga labeled microspheres are available. The method is applicable to daily routine and rendered clinically relevant informations.

EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer

Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.

Measurement of ocular lens ionizing radiation exposure after radioiodine therapy

AIM Current reports for the radiation cataracts contained a warning for deterministic effects at 1-2 Gy radiation single exposure for lens. Recently, the German Radiation Protection Board (SSK) published a document (234. SSK-Board) in that threshold dose for radiation cataracts is claimed at 0.5 Gy. The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and the International Commission on Radiological Protection (ICRP 103) has defined a limit of 150 mSv for its exposure.Recently, the ICRP lowered this limit down to 20 mSv per year.However, this limit does not apply to patients. Therefore, the question of the lens radiation exposure for patients underwent a radioiodine therapy (RIT) is a point at issue. PATIENTS, METHODS A total of 41 patients (age: 22-92 years) underwent a radioiodine therapy were included in the study. Optical stimulated luminescence dosimeters were used to measure the radiation exposure. The dosimeters were fastened nearby the patients eye lens. The measurement was carried out up to 48 h after radioiodine application and the patients were divided into three groups. Group 1: patients underwent a diagnostic 131I whole body scan (mean activity: 370 MBq); group 2: thyriod carcinoma patients under RIT (mean activity: 3700 MBq); group 3: hyperthyroid patients under RIT (activity: 180-1237 MBq). RESULTS The cumulative exposure of the eye lens during the stay at the therapy unit (48 h) was 4.8 ± 0.7 mGy in group 1, 24.5-50.5 mGy in group 2 and 2.7-26.3 mGy in group 3, respectively. For the calculation of the expected cumulative dose, including follow-up after patients dismissal, the effective half-lives were involved. The cumulative doses were obtained to be 6 ± 1 mGy in the first group, 63 ± 15 mGy in the second and 5-148 mGy in the third. CONCLUSION The results show that there exists a low risk for radiation cataract in a nuclear medicine therapy unit. After serial radioiodine therapies radiation-induced lens opacity cannot be expected.

[Therapy of bone metastases with radium-223. German guidelines].

This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.

Radionuklidtherapie von Knochenmetastasen mittels Radium-223

This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.

Quantitative evaluation of emission-computed tomography images based on fuzzy segmentation

Single photon emission computed tomography (SPECT) performs real 3D functional imaging in nuclear medicine. Even though the visual interpretation of nuclear medicine images by experienced physicians predominates in diagnostics the quantitative image analysis can reduce the subjective observer influences and offers the possibility for the use of objective numerical criteria. An essential problem of the quantitative evaluation of SPECT images is the determination of functional volumes from reconstructed SPECT data. This is the prerequisite for the estimation of the absolute radio nuclide concentration as a high level quantitation. In this paper we present a combined technique for the determination of functional volumes in SPECT data including elements of voxel based clustering methods and edge based fuzzy segmentation.

On the Reliability of Automatic Volume Delineation in Low-Contrast [(18)F]FMISO-PET Imaging.

Hypoxia is a marker of poor prognosis in malignant tumors independent from the selected therapeutic method and the therapy should be intensified in such tumors. Hypoxia imaging with positron emission tomography (PET) is limited by low contrast to noise ratios with every available tracer. In radiation oncology appropriate delineation is required to allow therapy and intensification. While manual segmentation results are highly dependent from experience and observers condition (high inter- and intra observer variability), threshold- and gradient-based algorithms for automatic segmentation frequently fail in low contrast data sets. Likewise, calibration of these algorithms using phantoms is not useful. Complex computational models such as swarm intelligence-based algorithms are promising tools for optimized segmentation results and allow observer independent interpretation of multimodal and multidimensional imaging data.