A. van Lingen

European semi-anthropomorphic spine phantom for the calibration of bone densitometers: Assessment of precision, stability and accuracy the European quantitation of osteoporosis study group

Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturers brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic “vertebrae” of different densities made of simulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.

Optimal metabolic conditions during fluorine-18 fluorodeoxyglucose imaging; a comparative study using different protocols

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) can identify viable myocardium in patients with coronary artery disease. Recently, FDG imaging with single-photon emission tomography (SPET) and 511-keV collimators has been described. To obtain optimal image quality in all patients, cardiac FDG studies should be performed during hyperinsulinaemic glucose clamping. It has been suggested that FDG imaging after the administration of a nicotinic acid derivative may yield comparable image quality to clamping. We studied eight patients and compared the image quality of cardiac FDG SPET studies after oral glucose loading, after administration of a nicotinic acid derivative (acipimox, 250 mg orally) and during hyperinsulinaemic glucose clamping. The image quality was expressed as the myocardial to blood pool (M/B) activity ratio, which is used as a measure of the target-to-background ratio The M/B ratios were comparable after clamping and acipimox (2.8±0.8 vs 2.9±0.7), whereas the M/B ratio was lower after oral glucose loading (2.2±0.3,P<0.05 vs clamp and acipimox). To determine the clearance of FDG from the plasma, blood samples were drawn at fixed time intervals and the FDG activity was measured in a gamma well counter. The FDG clearance was significantly lower after oral glucose loading (T1/2 oral load=16.2±5.7 min) as compared with clamping (T1/2 clamp=8.1±3.1 min) and acipimox (T1/2 acipimox=10.7±4.0 min, NS vs clamp,P<0.05 vs oral load). It may be concluded that FDG SPET imaging after acipimox administration yields image quality and clearance rates comparable to those obtained during clamping. FDG SPET in combination with acipimox may useful in clinical routine for the assessment of myocardial viability.

Radioimmunotargeting in ovarian carcinoma patients with indium‐111 labeled monoclonal antibody OV‐TL 3 F(ab′)2: pharmacokinetics, tissue distribution, and tumor imaging

Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies was studied in 28 patients suspected of having ovarian carcinoma, after i.v. administration of 1 mg F(ab′)2 fragments of the murine monoclonal antibody OV-TL 3, labeled with 150 MBq Indium-111. There were no adverse reactions, hematological and biochemical serum parameters were stable. In one patient a (subclinical) HAMA-response was found. Plasma clearance of the immunoconjugate was biphasic with half lives of t½}α = 1.4±0.8 h and t½}β = 25.1±3.7 h, resulting in an optimal time period for immunoscintigraphy at 24–48 h after administration. In 20 patients, undergoing extensive explorative surgery, a total of 271 samples of tumorous and normal tissues were analyzed for radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6 times (range 2.2–19.3) as high as the uptake in normal tissues (fat, peritoneum, muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that obtained with computer tomography, magnetic resonance imaging, ultrasonography and physical examination. While pelvic localizations were equally well detected by all methods, 48% of the abdominally located tumor deposits were correctly diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by CT-scanning and physical examination, and 6% by MRI. Immunoscintigraphy has potential as a diagnostic tool in ovarian cancer patients and biolocalization results justify further research into the therapeutic application of labeled monoclonal antibodies.

Absorbed dose distribution of the auger emitters 67Ga and 125I and the β-emitters 67Cu, 90Y, 131I, and 186Re as a function of tumor size, uptake, and intracellular distribution

PURPOSE The influence of tumor volume, uptake of radioactive compounds in cells of tumors and normal tissues, and characteristics of the emitted ionizing particles on the efficacy of systemic radiation were studied. METHODS AND MATERIALS The influence of these variables was assessed using a point kernel approach combined with a distance histogram technique. Simulation calculations were performed to assess dose distributions for three tumor sizes (phi = 200 microns, 2 mm, or 2 cm) and six radionuclides: 67Ga, 125I, 67Cu, 90Y, 131I, and 186Re. RESULTS The energy deposition patterns depended on the relation of the tumor size and range of the emitted particles. Selective uptake was especially important in cases where the range was short compared to the dimension of the tumor. CONCLUSION To attain a high dose for treatment of micrometastases, the use of Auger and conversion electron emitters (67Ga and 125I) or beta-emitters with emission spectra including low energetic electrons (67Cu and 131I) was recommended. The results demonstrated the complementary nature of selectivity of energy deposition and crossfire. This implied that for tumor cells or areas with reduced uptake, crossfire from radioactivity in surrounding cells or areas with selective uptake would be provided by intermediate (conversion electrons) or long-range (beta-particles) emissions.

Cardiac 18F-FDG-SPET studies in patients with non-insulin-dependent diabetes mellitus during hyperinsulinaemic euglycaemic clamping

Identification of viable myocardium is possible with 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). More recently, the feasibility of cardiac FDG imaging with single photon emission tomography (SPET) has been reported. In patients with diabetes mellitus, poor image quality is frequently obtained with FDG-PET, due to relative or absolute insulin deficiency and peripheral insulin resistance. To improve image quality of the FDG-PET studies, the hyperinsulinaemic glucose clamp has been proposed. We assessed the image quality of cardiac FDG-SPET studies in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and compared the results with those obtained in 10 patients without NIDDM. All FDG studies were performed during hyperinsulinaemic glucose clamping. Image quality was expressed as myocardial to blood pool activity (M/B) ratios. Residual viability was assessed in dysfunctional myocardium. The M/B ratios were comparable between patients with and without NIDDM (2.67 +/- 0.8 vs 2.50 +/- 0.7, N.S.). Residual viability was detected in 51% of the dysfunctional segments of the patients with NIDDM and in 49% of the segments of the patients without NIDDM. In the small subset of patients (n = 10) undergoing revascularization, 19 of 20 (95%) segments that had improved wall motion were viable on FDG-SPET. In contrast, 27 of 36 (75%) segments that did not improve were necrotic on FDG-SPET. Thus FDG-SPET during hyperinsulinaemic glucose clamping provides adequate image quality in patients with NIDDM compared with patients without NIDDM, and can be used in the detection of viable myocardium.

Volumetric measurements of bone mineral density of the lumbar spine: comparison of three geometrical approximations using dual-energy X-ray absorptiometry (DXA)

Measurements of bone mineral density using dual-energy X-ray absorptiometry (DXA) gives area values (g cm-2) rather than true volumetric values (g cm-3). To calculate the vertebral volume using planar postero-anterior and lateral DXA values, several different geometrical approximations were used: cubic, cylindrical with a circular cross-section and cylindrical with an elliptical cross-section. The aim of this study was to compare these geometrical approximations with each other and with a reference standard, defined as the volume found on a computed tomographic (CT) scan. L2 and L3 were evaluated in a phantom study. Volume approximations by the cube or cylinder with circular cross-section geometry showed more than a 50% overestimation (range 54-74%). However, the elliptical cylinder approach showed very good agreement: 2.1% and 1.2% for L2 and L3, respectively, when compared to the CT volumes. In addition, we performed four patient studies with both CT and DXA to evaluate the elliptical cylinder estimate in a clinical setting. For L2 and L3, the mean relative difference was less than 2%. We conclude that the elliptical cylinder approach results in the most accurate bone volume estimates in both the phantom and patients.

The elimination rate of 123I-heptadecanoic acid after intracoronary and intravenous administration

When calculating the elimination rate of radioactivity after the administration of radioiodinated heptadecanoic acid (123I-HDA), background correction is necessary due to the high level of background activity. In the present study, the subtraction method of Freundlieb et al. was investigated on validity. This was done by comparing the half-time values of the elimination rate after intravenous (i.v.) and intracoronary (i.c.) injection. In the latter case, no background correction was necessary. Six patients underoging cardiac catheterization were studied. Scintigraphy was performed after the injection of 123I-HDA into the left coronary artery and after i.v. injection. Half-time values were calculated from regions of interest drawn over myocardium perfused by the left-anterior descending branch (LAD) and the left circumflex artery (LCX). In the LAD region, the mean half-time value in the i.c. study was 22 min, while in the corrected i.v. study, the mean value was 27 min. In the LCX region, the half-time values were 24 and 33 min, respectively. The background-subtraction procedure proposed by Freundlieb et al. for i.v.-injected 123I-HDA ss incomplete, as it resulted in half-time values that were higher than those of the i.c. study.

Evaluation of heart-to-organ ratios of 123I-BMIPP and the dimethyl-substituted 123I-DMIPP fatty acid analogue in humans.

Radioiodinated fatty acid analogues modified by methyl-substitution are used for single photon emission tomography (SPET) imaging of the heart. The effect of mono- and dimethyl-substitution on heart-to-organ ratios was investigated in humans to evaluate their relative merits for SPET image quality. Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, 1 h after administration of 111 MBq 15-(p-[I-123]-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP, n = 7) or 111 MBq 15-(p-[I-123]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP, n = 4). Because these branched fatty acids are used for cardiac imaging, we focused on heart-to-organ (heart/organ) ratios by comparing small regions of interest in heart, liver, lung, muscle and bladder. Both tracers showed good visualization of the heart. DMIPP showed a relatively high liver uptake: the heart/liver ratios for DMIPP and BMIPP were 0.39 +/- 0.05 and 1.00 +/- 0.12, respectively (P < 0.0001). Increased lung activity was found for BMIPP, with a heart/lung ratio of 1.63 +/- 0.17 versus 2.32 +/- 0.28 for DMIPP (P < 0.001). In contrast to DMIPP, BMIPP also showed increased activity in the bladder. In conclusion, BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake affects cardiac SPET image quality and therefore BMIPP appears to provide superior cardiac SPET image quality in humans.

Validation of the histogram technique for three-dimensional and two-dimensional dosimetric calculations

Abstract Three-dimensional discrete dosimetric calculations were validated against an analytic approach for two simulated source distributions. The discrete approach was based on characterization of the source distribution by target-source distance histograms, including partial interval corrections. Using local submatrices and distance histograms, accurate dose rates were obtained for 90Y, 131I and 67Ga. Comparison of three- and two-dimensional calculations revealed that the latter were accurate, except for long range emitters.

A dosimetric model for intrathecal treatment with 131I AND 67GA

PURPOSE Calculations were performed of absorbed dose distributions of the beta-emitter 131I and the Auger emitter 67Ga for intrathecal administration. METHODS AND MATERIALS The proposed dosimetric model accounts for the macroscopic distribution of the activity, by means of a Medical Internal Radiation Dose Committee approach, and for the microscopic distribution of activity, by means of a point kernel technique. This point kernel approach was used in combination with a distance histogram technique, to study in more detail the absorbed dose distribution in the cerebro-spinal fluid, in the surface of the central nervous system, and in tumor sites. We simulated decreased uptake, as well as highly selective uptake in free-floating tumor cells and in meningeal lesions (1-16 cells thick). RESULTS In case of limited access to lesions adherent to the pia mater, the beta-emitter 131I provides crossfire from the CSF, resulting in a higher absorbed dose (Gy/MBq) in these lesions as compared with the Auger emitter 67Ga. In case of increasing radionuclide uptake, the increment of the absorbed dose in the adherent lesions and the free floating cells from 67Ga is considerable because of the local deposition of energy by this radionuclide. CONCLUSIONS The model might be useful to select the optimal emission characteristics of radionuclides applicable for intrathecal therapy, which is demonstrated in a comparison of the Auger emitter 67Ga and the beta-emitter 131I.