Arne Skretting

Breath Actuated Device Improves Delivery to Target Sites Beyond the Nasal Valve

Objectives: The objective was to compare nasal deposition patterns achieved with a conventional hand actuated spray pump and a novel breath actuated bidirectional prototype device housing the same spray pump (OptiMist™, OptiNose AS, Oslo, Norway).

Targeted Radiotherapy of Osteosarcoma Using 153Sm-Edtmp: A new promising approach

We report a case where targeted radionuclide therapy using 153Sm-EDTMP gave substantial palliative effect. A 35-year-old male with a primary osteosarcoma located in the first lumbar vertebra relapsed with progressive back pain after conventional treatment modalities had failed. He became bedridden, and developed paraparesis and impaired bladder function. On a diagnostic bone-scan intense radioactivity was localized in the tumor. He therefore was given 153Sm-EDTMP treatment twice, 8 weeks apart, 35 and 32 MBq/kg body weight respectively. After a few days the pain was significantly relieved and by the second radionuclide treatment the pareses subsided. For six months he was able to be up and about without any neurological signs or detectable metastases. Eventually, however, he experienced increasing local pain, developed paraparesis, was re-operated but died 4 months later. The dramatic transient improvement observed in this case warrants further exploration using 153Sm-EDTMP as a boost technique, supplementary to conventional external radiotherapy.

Nasal Deposition and Clearance in Man: Comparison of a Bidirectional Powder Device and a Traditional Liquid Spray Pump

BACKGROUND Delivery of powder formulations to the nose is an attractive alternative for many drugs and vaccines. This study compared the regional nasal deposition and clearance patterns of lactose powder delivered by the OptiNose powder device (Opt-Powder; OptiNose US Inc., Yardley, PA, USA) to that of liquid aerosol administered via a traditional hand-actuated liquid spray pump (Rexam SP270, Rexam Pharma, France). METHODS The study was an open-label, crossover design in seven healthy subjects (five females, two males). The regional nasal deposition and clearance patterns of the Opt-Powder device were compared to a traditional liquid spray pump by dynamic gamma camera imaging after administration of either (99m)Tc-labeled lactose powder or liquid (99m)Tc- diethelyne triamine pentaacetic acid-aerosol. The gamma camera images were scaled and aligned with sagittal magnetic resonance images to identify nasal regions. Possible deposition of radiolabeled material in the lungs following both methods of delivery was also evaluated. RESULTS Both powder and spray were distributed to all of the nasal regions. The Opt-Powder device, however, achieved significantly larger initial deposition in the upper and middle posterior regions of the nose than spray (upper posterior region; Opt-Powder 18.3% ± 11.5 vs. Spray 2.4% ± 1.8, p<0.02; sum of upper and middle posterior regions; Opt-Powder 53.5% ± 18.5 vs. Spray 15.7% ± 13.8, p<0.02). The summed initial deposition to the lower anterior and posterior regions for spray was three times higher compared to Opt-Powder (Opt-Powder 17.4% ± 24.5 vs. Spray 59.4% ± 18.2, p<0.04). OptiNose powder delivery resulted in more rapid overall nasal clearance. No lung deposition was observed. CONCLUSIONS The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions, whereas less was deposited in the lower regions. Overall nasal clearance of powder was slower initially, but due to retention in anterior nonciliated regions the overall nasal clearance after spray was slower.

Measurement of the ferric diffusion coefficient in agarose and gelatine gels by utilization of the evolution of a radiation induced edge as reflected in relaxation rate images.

A method has been developed to determine the diffusion coefficients of ferric ions in ferrous sulphate doped gels. A radiation induced edge was created in the gel, and two spin-echo sequences were used to acquire a pair of images of the gel at different points of time. For each of these image pairs, a longitudinal relaxation rate image was derived. From profiles through these images, the standard deviations of the Gaussian functions that characterize diffusion were determined. These data provided the basis for the determination of the ferric diffusion coefficients by two different methods. Simulations indicate that the use of single spin-echo images in this procedure may in some cases lead to a significant underestimation of the diffusion coefficient. The technique was applied to different agarose and gelatine gels that were prepared, irradiated and imaged simultaneously. The results indicate that the diffusion coefficient is lower in a gelatine gel than in an agarose gel. Addition of xylenol orange to a gelatine gel lowers the diffusion coefficient from 1.45 to 0.81 mm2 h-1, at the cost of significantly lower Rl sensitivity. The addition of benzoic acid to the latter gel did not increase the Rl sensitivity.

A simulation of MRI based dose calculations on the basis of radiotherapy planning CT images

Background. The advantage of MRI-based radiotherapy planning is the superior soft tissue differentiation. However, for accurate patient dose calculations, a conversion of the MR images into Hounsfield CT maps is necessary. The aim of the present study was to investigate the dose accuracy that can be achieved with segmented MR-images derived from the planning CT images by assigning fixed densities to different classes of tissues. Methods. Treatment plans for ten prostate cancer patients were selected. A collapsed cone algorithm was used to calculate patient dose distributions. The dose calculations were based on four different image sets: (1) the original CT-series (DDDP), (2) a simulated MR series with all tissue set to a homogenous water equivalent material of density 1.02 g/cm3 (DDW), (3) a simulated MR series with soft tissue set to a water equivalent material with density 1.02 g/cm3 and the bone set to a density of 1.3 g/cm3 (DDW+B1.3), and (4) a simulated MR series identical to (3) but with a bone density equal to 2.1 g/cm3 (DDW+B2.1). The dose distributions were compared by analysing dose difference histograms as well as through a visual display of spatial dose deviations. Results. The population based minimum, mean and maximum dose difference between the DDDP and DDW in the target volume was −2.8, −1.0 and 0.6%, respectively. Corresponding differences between DDDP and DDW+B1.3 were −1.6, 0.2 and 1.5%, respectively, and between DDDP and DDW+B2.1 −4.3, 4.2 and 9.7%, respectively. For the rectum, the differences between CTDP and the other image sets were in the range of −19.5 to 8.8%. For the bladder, the differences were in the range of −9.6 to 7.0%. Conclusions. A systematic study using segmented MR images was undertaken. To achieve an acceptable accuracy in the CTV dose, the MR images should be segmented into bone and water equivalent tissue. Still, significant dose deviation for the organs at risk may be present. As tissue segmentation in real MR images is introduced, segmentation errors and errors that stem from geometrical non-linearities may further reduce the accuracy.

Integrin scintimammography using a dedicated breast imaging, solid‐state γ‐camera and 99mTc‐labelled NC100692

Objective:  Integrin scintimammography with NC100692 and a dedicated γ‐camera, LumaGEM, based on semi‐conductor technology, was performed to investigate the detection ability of this combination in breast cancer.

Measurement of dynamic wedge angles and beam profiles by means of MRI ferrous sulphate gel dosimetry

The purpose of this study is to examine the possible value of measuring the dose distribution in dynamic wedge photon beams using ferrous sulphate gel phantoms analysed by MRI. The wedge angles and dose profiles were measured for a field size of 70 x 70 mm2 and for dynamic wedge angles of 15 degrees, 30 degrees, 45 degrees and 60 degrees using a 15 MV photon beam generated from a Clinac 2100 CD (Varian). The dose profiles obtained from MRI ferrous sulphate gel were in good agreement with the dose measurements performed with a diode detector array. Also, the wedge angles determined from the MRI ferrous sulphate gel agreed well with the values obtained by using film dosimetry and with calculations by use of TMS (treatment planning system) (Helax, Uppsala, Sweden). The study demonstrated that MRI ferrous sulphate gel dosimetry is an adequate tool for measurements of some beam characteristics of dynamic radiation fields.

Intratumour heterogeneity in the uptake of macromolecular therapeutic agents in human melanoma xenografts

Intratumour heterogeneity in the uptake of blood-borne technetium-labelled human serum albumin (99mTc-HSA) was studied in human melanoma xenografts in an attempt to identify transport barriers leading to inadequate and heterogeneous uptake of macromolecular therapeutic agents in tumours. The Bioscope imaging system, which can detect the distribution of 99mTc in 10-μm-thick tissue sections with a spatial resolution of just above 50 μm, was used to image the 99mTc-HSA uptake. Xenografted tumours of four human melanoma cell lines were included in the study. Significant intratumour heterogeneity in the uptake of 99mTc-HSA was detected. The heterogeneity had two distinctly different components, one random and one radial component. The uptake was lowest in the centre of the tumours and increased towards the tumour periphery. This radial heterogeneity was superimposed by a random heterogeneity, that is, spots with high uptake colocalised with spots with high vascular density and regions without significant uptake colocalised with necrotic regions. The magnitude of the heterogeneity did not change significantly with time after the administration of 99mTc-HSA. The tumours showed a random and a radial heterogeneity in blood perfusion similar to that in the uptake of 99mTc-HSA. The observations reported here suggest that the intratumour heterogeneity in the distribution of 99mTc-HSA was initiated primarily because of heterogeneity in the supply of 99mTc-HSA through the microvasculature, and that the presence of severe transport barriers in the tumour interstitium prevented significant equalisation of the initial heterogeneity with time. Consequently, strategies for improving the delivery of macromolecular therapeutic agents to tumours should focus on increasing the tumour blood perfusion to increase the total uptake and improving the diffusion conditions in the tumour interstitium to diminish the heterogeneity in the uptake.

Radionuclide therapy with bone-seeking compounds: Monte Carlo calculations of dose-volume histograms for bone marrow in trabecular bone

The purpose of the present work was to investigate how haematopoietic stem cell survival is affected by the differences in the dose distribution that arise from different radionuclides contained in bone-seeking radiopharmaceuticals. This was carried out in three steps: (a) calculations of representative dose distributions in individual bone marrow cavities that are irradiated by sources of 89Sr, 186Re, 117mSn or 153Sm, uniformly distributed on the bone surfaces; (b) assessment of the corresponding haematopoietic stem cell survival and (c) a comparison of these results with results obtained using the assumption of a uniform dose distribution. Two different idealized models of the geometry of trabecular bone were formulated, each consisting of an infinite array of identical elements. Monte Carlo simulations were used to generate dose-volume histograms that were used to assess haematopoietic stem cell survival with two different assumptions about spatial cell distributions. Compared with a homogeneous dose distribution, the estimated cell survival was markedly higher for 117mSn and 153Sm, and only slightly different for 89Sr and 186Re. The quantitative results differed between the two geometric models and the assumptions about spatial cell distribution, but the trends were the same. The results imply that it is necessary to include dose distributions for individual bone marrow cavities in considerations concerning bone marrow toxicity.

'Intensity diffusion' is a better description than 'partial volume effect'

Dear Sir, The term ‘partial volume effect’ (PVE) has frequently been used in nuclear medicine 3D imaging to describe the effects of blurring of an ideal PET or SPECT activity distribution by a point spread function [1–3] .The term was first introduced as a description of the artefact that arose in CT images when a structure (usually bone) was partially covered by the scanning X-ray beam. The resulting reconstructed image would then show this structure but with an erroneous Hounsfield number assigned to it and often with a distorted form. The concentration of activity can vary significantly within an organ and even within a voxel. It is therefore a lack of precision to talk of the volume that the activity occupies or the ‘tissue fractions’ of the voxel volume [3]. In order to understand all the implications of image formation it is necessary to describe nuclear medicine 3D imaging (SPECT and PET) in a totally different way. One solution is to introduce the term ‘intensity diffusion’ in analogy to the physical process of diffusion. If one deposits a very small volume -a sourceof a diffusible substance (consisting of equal molecules) within a gel the molecules will move randomly so that their concentration form a continuous 3D gaussian distribution with the width (in nuclear medicine the FWHM) depending on time and magnitude of the diffusion coefficient. If there were several small such sources diffusion would lead to a superposition in space of contributions from each of them. Finally, one could image to cut the gel into regular cubes (voxels) and count the molecules within each of them. This is a very close analogy to nuclear medicine 3D imaging although the image is formed as a result of a computer algorithm. The 3D point spread function can be though to act on the activity distribution before the volume is subdivided into voxels of finite size and counts integrated for each of these. This description would explain the lack of counts recovery for small volumes, the ‘spill in’ and ‘spill out’ (3) from/to voxels etc. If one considers an intense point source with a spatial extent of one micrometer there would be no partial volume but still contributions to neighbouring voxels. Description of PET and SPECT imaging as an ‘intensity diffusion’ also serves to explain some phenomena associated with image intensity: The spread of intensity is such that the maximal signal decreases while the total intensity integrated over a larger volume is maintained. This description would also clarify to non-nuclear medicine referring physicians a frequently met misunderstanding: that the low spatial resolution power makes it impossible to detect a source of sub-millimeter size. If the source carries enough activity, it is seen alright but its intensity diffuses into neighbouring voxels. Furthermore, the effects of smoothing with a 3D gaussian filter during reconstruction of a PET image series (as is for instance done on the Siemens Biograph series) may be considered a further diffusion of intensity: Choice of an increasingly wider smoothing filter makes the maximum signal (and thus the SUV) from small tumours decrease (admittedly the noise decreases as well). With good accuracy the resulting width of the point spread function may be calculated exactly as one would calculate the effects of further diffusion of the molecules in the gel: by adding the squares of the FWHM of the intrinsic resolution and gaussian filter to form the square of the resulting system FWHM. Mathematically, the reconstructed image intensity distribution can be described Eur J Nucl Med Mol Imaging (2009) 36:536–537 DOI 10.1007/s00259-008-1032-6