Bone regeneration induced by a 3D architectured hydrogel in a rat critical-size calvarial defect.

Bone regeneration can be stimulated by implantation of biomaterials, which is especially important for larger bone defects. Here, healing potency of the porous ArcGel was evaluated in a critical-size calvarial bone defect in rats in comparison with clinical standard autologous bone and Bio-Oss® Collagen (BioOss), a bone graft material frequently used in clinics. Bone healing and metabolic processes involved were monitored longitudinally by [18F]-fluoride and [18F]-FDG µ-PET/CT 1d, 3d, 3w, 6w, and 12w post implantation. Differences in quality of bone healing were assessed by ex vivo µ-CT, mechanical tests and histomorphometry. The amount of bone formed after implantation of ArcGel was comparable to autologous bone and superior to BioOss (histomorphometry). Furthermore, microarchitecture of newly formed bone was more physiological and better functional in case of ArcGel (push-out tests). [18F]-FDG uptake increased until 3d after implantation, and decreased until 12w for both ArcGel and BioOss. [18F]-fluoride uptake increased until 3w post implantation for all materials, but persisted significantly longer at higher levels for BioOss, which indicates a prolonged remodelling phase. The study demonstrates the potential of ArcGel to induce restitutio ad integrum comparable with clinical standard autologous bone and better bone regeneration in large defects compared to a commercial state-of-the-art biomaterial.

Target development for diversified irradiations at a medical cyclotron.

The irradiation facility at an old medical cyclotron (Ep=17 MeV; Ed=10 MeV) was upgraded by extending the beam line and incorporation of solid state targetry. Tests performed to check the quality of the available beam are outlined. Results on nuclear data measurements and improvement of radiochemical separations are described. Using solid targets, with the proton beam falling at a slanting angle of 20°, a few radionuclides, e.g. (75)Se, (120)I, (124)I, etc. were produced with medium currents (up to 20 µA) in no-carrier-added form in quantities sufficient for local use. The extended irradiation facility has considerably enhanced the utility of the medical cyclotron.

Evaluation of excitation functions of 100Mo(p,d+pn)99Mo and 100Mo (p,2n)99mTc reactions: Estimation of long-lived Tc-impurity and its implication on the specific activity of cyclotron-produced (99m)Tc.

Excitation functions were calculated by the code TALYS for 10 proton-induced reactions on (100)Mo. For (100)Mo(p,d+pn)(99)Mo and (100)Mo(p,2n)(99m)Tc, calculations were also performed using the code STAPRE. Furthermore, for those two reactions and (nat)Mo(p,x)(96)Tc, evaluation of available experimental data was also carried out. The production of (99m)Tc via the (100)Mo(p,2n)-process is discussed. The ratio of atoms of long-lived (99g)Tc and (98)Tc to those of (99m)Tc is appreciably higher in cyclotron production than in generator production of (99m)Tc; this may adversely affect the preparation of (99m)Tc-chelates.

[Perfusion brain imaging with SPECT-technique. German Guideline S1]. / Hirnperfusions-SPECT mit 99mTc-Radiopharmaka. DGN-Handlungsempfehlung (S1-Leitlinie).

This paper describes the guideline for perfusion brain imaging with SPECT-technique published by the Association of the Scientific Medical Societies in Germany (AWMF).The purpose of this guideline is to provide practical assistance for indication, examination procedures, findings and their interpretation also reflecting the present state of the art. Information and instruction are given regarding indication, preparation of the patients and examination procedures of brain perfusion SPECT, including preparation and quality control of the tracer as well as the radiation dosimetry, technical performance of image acquisition with the gamma-camera and image processing. Also advices for interpretation of findings are given. In addition, possible pitfalls are described.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

Excitation functions of α-particle induced reactions on enriched 123Sb and (nat)Sb for production of 124I.

Excitation functions of (α,xn) reactions on 98.28% enriched (123)Sb and on (nat)Sb were measured from 9 to 40 MeV. The data could be described well in terms of statistical and precompound models using the code TALYS. The discrepancies in the literature data for the formation of (125)I and (126)I were solved. The nuclear reaction (123)Sb(α,3n)(124)I on an enriched target appears to be interesting for the production of (124)I (T(1/2)=4.18 d) over the energy range E(α)=42→32 MeV, its yield being 11.7 MBq/µAh. The levels of the radionuclidic impurities (125)I and (126)I amount to 1.8% and 0.6%, respectively. The use of (nat)Sb as target material for (124)I production is unsuitable due to the high level of (123)I impurity.

Fluorine-18 radiopharmaceuticals beyond [18F]FDG for use in oncology and neurosciences.

Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 ((18)F) tracers that can be used for PET studies in the fields of oncology and neurosciences. However, most of the (18)F-tracers other than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) are in less than optimum human use and there is considerable scope to bring potentially useful (18)F-tracers to clinical investigation stage. The International Atomic Energy Agency (IAEA) convened a consultants' group meeting to review the current status of (18)F-based radiotracers and to suggest means for accelerating their use for diagnostic applications. The consultants reviewed the developments including the synthetic approaches for the preparation of (18)F-tracers for oncology and neurosciences. A selection of three groups of (18)F-tracers that are useful either in oncology or in neurosciences was done based on well-defined criteria such as application, lack of toxicity, availability of precursors and ease of synthesis. Based on the recommendations of the consultants' group meeting, IAEA started a coordinated research project on "Development of (18)F radiopharmaceuticals (beyond [(18)F]FDG) for use in oncology and neurosciences" in which 14 countries are participating in a 3-year collaborative program. The outcomes of the coordinated research project are expected to catalyze the wider application of several more (18)F-radiopharmaceuticals beyond FDG for diagnostic applications in oncology and neurosciences.

Radiochemical determination of cross sections of alpha-particle induced reactions on 192Os for the production of the therapeutic radionuclide 193mPt.

For determination of cross sections of alpha-particle induced reactions on 99.65% enriched (192)Os, the methods for electrolytic preparation of thin samples and radiochemical separation of radioplatinum were optimized. The excitation functions of the (192)Os(alpha,n)(195m)Pt and (192)Os(alpha,3n) (193m)Pt reactions were measured from 20 to 39 MeV. The cross section of the latter reaction reaches a maximum value of about 1.5b at an energy around 36 MeV. The results of nuclear model calculations using the codes TALYS and STAPRE agreed well with the measured data. The optimum energy range for the production of no-carrier-added (193m)Pt (T(1/2)=4.33 d) was found to be E(alpha)=40-->30 MeV. The thick target yield amounts to 10 MBq/microA h and a possible batch yield of 2 GBq should be sufficient for Auger electron therapy on a wide scale.

Excitation function of the 192Os(3He,4n)-reaction for production of 191Pt.

In search of an alternative production route of the therapeutically and environmentally interesting radionuclide (191)Pt (T(1/2)=2.8 d), excitation function of the (192)Os((3)He,4n)(191)Pt reaction was measured from its threshold up to 36 MeV. Thin samples of enriched (192)Os were prepared by electrodeposition on Ni-foils, and the conventional stacked-foil technique was used for cross-section measurements. The experimental data were compared with the results of theoretical calculations using the codes ALICE-IPPE and TALYS. Good agreement was found with TALYS. The theoretical thick target yield of (191)Pt over the energy range E(3He)=36-->25 MeV amounts to 6.7 MBq/microA h. A comparison of various investigated production methods of (191)Pt is given. The here investigated (192)Os((3)He,4n)-process leads to very high-purity (191)Pt (>99.5%).

Production of the therapeutic radionuclides 193mPt and 195mPt with high specific activity via alpha-particle-induced reactions on 192Os.

For the production of therapy-relevant radionuclides (193m)Pt (T(1/2)=4.33 d) and (195m)Pt (T(1/2)=4.03 d) with a high specific activity, the (192)Os(alpha,n)(195m)Pt and (192)Os(alpha,3n)(193m)Pt nuclear reactions were investigated for the first time from their respective thresholds up to 28 MeV. Thin samples of enriched (192)Os were prepared by electrodeposition on Ni, and the conventional stacked-foil technique was used for cross-section measurements. The calculated thick target yields were found to be 0.013 MBq/microA h for the (192)Os(alpha,n)(195m)Pt reaction in the energy range of E(alpha)=24-->18 MeV, and 0.25 MBq/microA h for the (192)Os(alpha,3n)(193m)Pt reaction in the energy range of E(alpha)=28-->24 MeV. The two radionuclides could not be detected in the interactions of (3)He particles with (192)Os. A production method involving high-current alpha-particle irradiation of enriched (192)Os and efficient chemical separation of radioplatinum was developed. Batch yields of about 1 MBq (195m)Pt and 8.7 MBq (193m)Pt were achieved. Compared to the reactor production these batch yields are very low, but the (192)Os(alpha,n)(195m)Pt and (192)Os(alpha,3n)(193m)Pt reactions are superior with respect to the specific activity of the products which is higher by two orders of magnitude.

PET imaging problems with the non-standard positron emitters Yttrium-86 and Iodine-124.

AIM: Positron emission tomography (PET) imaging of non-standard positron emitters is influenced by gamma-coincidences, i.e. false coincidences produced by the coincident detection of an annihilation photon and a gamma-ray simultaneously emitted with the positron. The extent to which the PET study is disturbed by this effect is dependent on the kind of the positron emitter used, the kind and position of the object, the acquisition mode, i.e. the optional use of septa, and the reconstruction program. In order to demonstrate and study imaging problems with non-standard positron emitters, a phantom was scanned containing non-radioactive rods with different absorption materials and filled with either (124)I or (86)Y in the bidimensional (2D) as well as tridimensional (3D) acquisition mode. METHODS: For reconstruction, the PET manufacturer's standard software without any modification was used. To reduce errors caused by the gamma-coincidences, a simple linear background subtraction, estimated from the counts at the scanner's external radius, was applied. RESULTS: Without background subtraction, apparent positive and negative ''radioactivity concentrations'' were found in regions of interest positioned over the non-radioactive rods with values higher for (86)Y compared to (124)I and also higher for 3D compared to 2D. A complete subtraction of the background led to erroneous RESULTS: The errors in the phantom's non-radioactive rods and the difference between measured and true radioactivity became minimum, when about 75% of the background was subtracted. This refers to both the 2D and 3D mode. CONCLUSION: Quantitation problems with the non-standard positron emitters (124)I and (86)Y could be minimized in the phantom study examined here by using a simple background subtraction together with the manufacturer's standard correction and reconstruction procedures.

Excitation functions of natGe(p,xn)71,72,73,74 As reactions up to 100 MeV with a focus on the production of 72 As for medical and 73 As for environmental studies.

Excitation functions for the formation of the arsenic radionuclides (71)As, (72)As, (73)As and (74)As in the interaction of protons with (nat)Ge were measured from the respective threshold energy up to 100 MeV. The conventional stacked-foil technique was used and the needed thin samples were prepared by sedimentation. Irradiations were done at three cyclotrons: CV 28 and injector of COSY at Forschungszentrum Jülich, and Separate Sector Cyclotron at iThemba LABS, Somerset West. The radioactivity was measured via high-resolution gamma-ray spectrometry. The measured cross section data were compared with the literature data as well as with the nuclear model calculations. In both cases, the results generally agree but there are discrepancies in some areas, the results of nuclear model calculation and some of the literature data being somewhat higher than our data. The integral yields of the four radionuclides were calculated from the measured excitation functions. The beta(+) emitting nuclide (72)As (T(1/2)=26.01 h) can be produced with reasonable radionuclidic purity ((71)As impurity: <10%) over the energy range E(p) = 18-->8 MeV; the yield of 93 MBq/microAh is, however, low. The radionuclide (73)As (T(1/2)=80.30 d), a potentially useful indicator in environmental studies, could be produced with good radionuclidic purity ((74)As impurity: <11%) over the energy range E(p) = 30 --> 18 MeV, provided, a decay time of about 60 days is allowed. Its yield would then correspond to 2.4 MBq/microAh, and GBq amounts could be produced when using a high current target.

Excitation functions of (alpha,xn) reactions on (nat)Rb and (nat)Sr from threshold up to 26 MeV: possibility of production of (87)Y, (88)Y and (89)Zr.

Excitation functions were measured by the stacked-foil technique for (nat)Rb(alpha,xn)(87m,87m+g,88)Y and (nat)Sr(alpha,xn)(86,88,89)Zr reactions from their respective thresholds up to 26 MeV. The samples for irradiation were prepared by sedimentation and pellet pressing techniques. The measured data were compared with those available in the literature. From the excitation functions, integral yields of the products were calculated. The suitable energy ranges for the production of (87)Y and (88)Y via (nat)Rb(alpha,xn) processes and of (89)Zr via the (nat)Sr(alpha,xn) process are E(alpha)=26-->20 MeV, E(alpha)=26-->5 MeV and E(alpha)=20-->8.5 MeV, respectively. The respective yields amount to 8.2, 0.08 and 0.9 MBq/microA h. Production of (88)Y is feasible if a waiting time of about 2 months is allowed to let the impurities decay out. Also, (87)Y can be produced with a relatively low impurity of (88)Y. The yields of both (88)Y and (87)Y via the present routes are, however, appreciably lower than those via the (nat)Sr(p,xn) processes. There is a possibility to produce (89)Zr via the alpha-particle irradiation of (nat)Sr. The yield is rather low but would be considerably increased if enriched (86)Sr would be used as target material. The radionuclidic impurity levels in all the three products are discussed.

Evaluation of novel tropane analogues in comparison with the binding characteristics of [18F]FP-CIT and [131I]beta-CIT.

This study evaluated novel potential dopamine transporter (DAT) inhibitors as ligands for positron emission tomography. Five new tropane analogs were synthesized and compared with the known ligand 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) and the recently characterized ligands N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)-nortropane (PE2I) and 2beta-carbofluoroethoxy-3beta-(4-methylphenyl)tropane (FETT). Evaluation with autoradiography measured the ability to antagonize the binding of [(131)I]iodine-labeled beta-CIT and [(18)F]fluorine-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodo-phenyl) nortropane in rat and pig brains. The standards for comparison (PE2I and FETT) competed strongly in all regions investigated (striatum, cortex, superior colliculus and cerebellum). Of the new compounds, 2alpha-amido-fluoroethyl-3beta-(4-iodophenyl)tropane (4) and 2beta-amido-fluoroethyl-3beta-(4-iodophenyl)tropane (4a) competed strongly with [(131)I]beta-CIT in DAT-rich striatum, but also in other brain regions suggesting poor DAT selectivity. Because [(131)I]beta-CIT binds unselectively both to DAT and serotonin transporters, no definite conclusion about the selectivity of the new compounds is possible. However, preclinical studies using the compounds and labeled with fluorine-18 or iodine-131 are encouraged.

Yield and purity of 82Sr produced via the natRb(p,xn) 82Sr process.

The recently reported cross-section data for the production of 82Sr via the natRb(p,xn) 82Sr process were evaluated. For the natRb(p,xn) 85Sr process, cross-sections were measured experimentally over the proton energy range of 25-45 MeV, a region where very few data existed. An evaluation of the recently published data on the formation of 85Sr was then also performed. From the recommended data curves, the integral yields of the desired radionuclide 82Sr and the impurity 85Sr were calculated. Yields were also determined experimentally over several energy ranges using thick natRbCl targets. The experimental and calculated yields were found to be in agreement within 15%. These integral tests add confidence to the evaluated cross-section data. For the production of 82Sr, an incident proton energy of 60 MeV or above is recommended; the 85Sr impurity then corresponds to <20%.

Fluorine-18 labeling methods: Features and possibilities of basic reactions.

Many experimental and established tracers make fluorine- 18 the most widely used radionuclide in positron emission tomography with an increasing demand for new or simpler 18F-labeling procedures. After a brief summary of the advantages of the nuclide and its major production routes, the basic features of the principal radiofluorination methods are described. These comprise direct electrophilic and nucleophilic processes, or in case of more complex molecules, the labeling of synthons and prosthetic groups for indirect built-up syntheses. While addressing the progress of no-carrier-added 18F-labeling procedures, the following chapters on more specific topics in this book are introduced. Emphasis is given to radiofluorination of arenes--especially with iodonium leaving groups. Examples of radiopharmaceutical syntheses are mentioned in order to illustrate strategic concepts of labeling with fluorine-18.

Assessment of the short-lived non-pure positron-emitting nuclide (120)I for PET imaging.

PURPOSE: The non-pure positron-emitting iodine isotope (120)I (T(1/2)=81 min) is a short-lived alternative to (124)I. (120)I has a positron abundance more than twice that of (124)I and a maximum positron energy of 4 MeV. This study was undertaken to evaluate and characterise the qualitative and quantitative PET imaging of (120)I. METHODS: (120)I was produced via the (120)Te(p,n) reaction on highly enriched (120)Te. The measurements were done with the Siemens scanner HR+ and the 2D PET scanner GE PC4096+. A cylinder containing three cold inserts and a phantom resembling a human brain slice were used to evaluate half-life, positron abundance and background correction. To analyse the image resolution, a -mm tube placed in water was filled with (120)I and (18)F. Comparisons with (18)F, (124)I and (123)I (measured with SPECT) were made using the Hoffman 3D brain phantom. RESULTS: The half-life of 81.1 min was reproduced by the PET measurements. The PET-based positron abundance ranged from 47.9% to 55.0%. The reconstructed image resolution found with the HR+ was 5.4 mm FWHM (12.3 mm FWTM), in contrast to 4.6 mm (8.6 mm) when using (18)F. Erroneous positive and negative numbers of radioactivity found in the cold inserts became nearly zero when the background of gamma-coincidences was corrected for. Images of the Hoffman phantom were inferior to those obtained when (18)F or (124)I was applied but superior to the (123)I-SPECT images. CONCLUSION: Our data show that (120)I of high radionuclidic purity can be regarded as a suitable nuclide for the PET imaging of radioiodine-labelled pharmaceuticals.

No-carrier-added nucleophilic 18F-labelling in an electrochemical cell exemplified by the routine production of [18F]altanserin.

A new type of electrochemical cell with anodic deposition of no-carrier-added [(18)F]fluoride and variable reaction volume has been developed. The reactor is designed for small reaction volumes and non-thermal drying of [(18)F]fluoride. The implementation of this reactor into a complete remotely controlled synthesis device is described for the routine production of [(18)F]altanserin. A radiochemical yield of 23+/-5% was obtained via cryptate-mediated nucleophilic (18)F-fluorination. Batches of up to 6 GBq [(18)F]altanserin, suitable for human application, with a molar activity of >500 GBq/micromol were obtained within 75 min.