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PubMed1997

[Preoperative localization in primary hyperparathyroidism: value of Tc-99m-MIBI scintigraphy].

In order to assess the value of scanning with 99mTc-MIBI before surgery in primary hyperparathyroidism (PHP), we performed this procedure in 30 patients with PHP. MIBI imaging findings were: 24 true positive results, three false positive, three false negative (sensitivity: 89%). The 24 true positive results comprised 21 solitary adenomas (one of which was ectopic), one cancer, and two parathyroid hyperplasias. Thus 99mTc-MIBI scanning seems to be useful for the preoperative localization, and for preparing the surgeon to unusual features that could generate surgical failure.

Adenoma↗
PubMed1983

The qualitative I-131 Hippuran renogram. A potential problem.

The I-131 Hippuran renogram time activity curve is usually generated by assigning computer assisted regions of interest over each kidney. Qualitative whole kidney renogram curves can be misleading when there is a nonobstructed but dilated collecting system or asymmetrical excretion of the tracer from the renal collecting system. This problem can be minimized by generating an additional renogram curve from a region of interest assigned over each renal cortex.

Adult↗
PubMed2006

Nuclear medicine procedures for the diagnosis of acute and chronic renal failure.

The focus of this review is on the current role of nuclear imaging studies in the clinical evaluation of patients with acute and chronic renal failure. In this setting nuclear imaging has two roles: diagnostic and prognostic, indicating that these methods are an essential component in the evaluation of renal diseases. The functional assessment of the kidney by nuclear medicine procedures is based on the use of radioisotopes bound to non-metabolized molecules with known pharmacokinetics. Renal scintigraphy is usually applied for the assessment of renal function expressed as glomerular filtration rate, effective renal plasma flow or more generally kidney perfusion. Newer methods rely on positron emission tomography, which allows the generation of images with higher resolution and absolute quantitation of biological processes such as transport activities, enzyme activities or angiotensin receptors.

Acute Kidney Injury↗
PubMed1994

Single breath diffusing capacity for carbon monoxide in stable asthma.

BACKGROUND: Single breath diffusing capacity for carbon monoxide (Dco) is commonly used as a simple method of assessing overall pulmonary gas exchange properties. Studies of Dco in bronchial asthma have yielded conflicting results. OBJECTIVE: To study Dco and to determine the factors influencing Dco in patients with asthma. METHODS: Dco was prospectively measured in 80 consecutive never-smoker patients with uncomplicated stable asthma. The topographic distribution of lung perfusion was determined in 10 asthmatics and 10 controls, with a 133Xe radionuclide scan. RESULTS: The mean (SD) value of Dco was increased to 117 (17) percent of predicted values; individual values were either within or above normal limits; diffusion was also elevated at 116 (19) percent after correction for alveolar volume (transfer coefficient, D/VA). The Dco was not correlated with atopic status, duration of asthma, or results of spirometric tests; there was a weak negative correlation between D/VA and FEV1 or residual volume. There was a better perfusion of the upper zones of the lungs in asthmatics as compared with controls. Among the asthmatics, there was a strong positive correlation between Dco and the apex to base perfusion ratio (r = 0.975). CONCLUSIONS: Dco is normal or high among never smoker patients with uncomplicated asthma; elevated Dco may be attributed to a better perfusion of the apices of teh lungs; the latter could result from two mutually nonexclusive mechanisms: an increase in pulmonary arterial pressure and/or a more negative pleural pressure generated during inspiration as a consequence of bronchial narrowing. The unexpected finding of high Dco should raise the possibility of bronchial asthma in patients with otherwise undiagnosed conditions.

Adult↗
PubMed2007

Radiation dose distribution in human kidneys by octreotides in peptide receptor radionuclide therapy.

UNLABELLED: Ex vivo autoradiographs of healthy kidney tissue from patients who received (111)In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) before nephrectomy showed very heterogeneous radioactivity patterns in the kidneys. The consequences of the reported inhomogeneities have been evaluated for radionuclide therapy with (90)Y- DOTA-Tyr(3)-octreotide (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), (177)Lu-DOTA-Tyr(3)-octreotate, and (111)In-DTPA-octreotide by calculating dose distributions and dose-volume histograms (DVHs) for the kidneys. METHODS: Monte Carlo radiation transport calculations were performed by using the MCNP code version 5. The autoradiography data were used in a 2-dimensional model of the kidney tissue sections. A voxel structure inside the MIRD Pamphlet 19 multiregion kidney model was developed to generate a 3-dimensional representation of the autoradiographs. Dose distributions were calculated for the beta-emitter (90)Y, the low-energy electron and gamma-emitter (111)In, and the beta- and gamma-emitter (177)Lu. Isodose curves were generated for the 2-dimensional kidney sections and DVHs for the 3-dimensional kidney model. RESULTS: The isodose curves for the high-energy beta-emitter (90)Y did not show a sign of the inhomogeneous activity distribution, apart from the cortex-medulla boundaries. Both (111)In and (177)Lu isodose curves follow the autoradiographic activity distribution exactly. The 2 gamma-rays from (111)In give higher doses to the low-radioactivity regions in the kidney sections. The DVHs show that the inhomogeneous activity distribution creates considerable volumes within the kidney and within the cortex with lower doses than the average kidney dose, together with volumes receiving much higher doses. This effect is most profound for (177)Lu, but also (111)In shows this heterogeneity in the dose distribution. CONCLUSION: Kidney dosimetry for radionuclide therapy can be based on average MIRD-based dose models for high-energy beta-emitters (such as (90)Y). In contrast, low-energy beta-emitters (such as (177)Lu) and Auger-electron-emitting radionuclides (such as (111)In) produce dose distributions in the kidneys that are very dependent on the activity distribution pattern in the kidney or renal cortex. Complication probability models for renal tissue damage after radionuclide therapy with these latter nuclides need to be developed, as the existing models based on average dose to the kidney or cortex from external beam therapy experience are most probably not valid.

Dose-Response Relationship, Radiation↗
PubMed2003

Application of artificial neural network algorithm to detection of parathyroid adenoma.

BACKGROUND: The most common radionuclide procedures for parathyroid imaging are (99m)Tc-MIBI/ (99m)Tc pertechnetate subtraction scintigraphy and (99m)Tc-MIBI double-phase imaging, with estimation of MIBI wash-out rate. Those two methods are by some authors regarded as complementary techniques, yielding the best evaluation of parathyroid gland if performed conjointly. By such an approach it seems reasonable to substitute the visual assessment of neck scintigrams and semiquantitative evaluation of MIBI wash-out rate with a single, common procedure. The aim of this study was application of the Artificial Neural Network (ANN) simulated by the computer program to detection and localisation of pathological parathyroid tissue in the planar neck scintigrams. MATERIAL AND METHODS: The applied algorithm was based on simultaneous data processing in sets of 3 single pixels, each of them belonging to one of the three consecutive neck scintigrams generated 20 min. after (99m)TcO(4 )- administration, 10 min. after (99m)Tc-MIBI injection and 120 min. after (99m)Tc-MIBI injection, respectively. Those scintigrams were aligned which each other according to the same vertical and horizontal co-ordinates. The training patterns were obtained from 25 patients by searching for maximum count numbers within small ROIs drawn in selected scintigraphic areas, arbitrarily classified and coded in a numerical scale. In 10 pts the results of ANN simulation were compared with those obtained by common conventional assessment of two radionuclide parathyroid examinations: subtraction method and (99m)Tc-MIBI double-phase imaging. RESULTS: The training patterns processed by the neural network showed a close relationship with the results of visual assessment of original neck scintigrams, with R square coefficient R(2) = 0.717, and standard error equal to 0.243. Similar comparison between original data and results of multidimensional regression analysis yielded weaker relationship, with R(2) = 0.543 and standard error 0.567. Parametric images obtained by the neural network presented regions with homogeneously distributed, relatively high activity, greater than or equal to 750 cts/pixel, visualized in areas of confirmed abnormal parathyroid location. In all 10 patients with suspected parathyroid adenoma results obtained by ANN simulation agreed with those by conventional methods. In five of these cases no parathyroid abnormalities were found. In the remaining 5 subjects results of both approaches were positive but the abnormalities were depicted more distinctly and visualised more clearly in parametric images received by ANN than in original scans. CONCLUSIONS: Application of trained ANN enables objective and quantitative detection and localisation of parathyroid adenoma and is a good alternative for conventional radionuclide imaging procedures used in diagnosing parathyroid abnormality. Including in neural network simulation not only scintigraphic data, but also clinical symptoms and/or some other indicators of parathyroid abnormality, parathormone level first of all, should be a next step in developing a procedure for assessing parathyroid abnormality, of high diagnostic accuracy.

Adenoma↗
PubMed2005

Radioactivity evaluation for the KSTAR tokamak.

The deuterium-deuterium (D-D) reaction in the KSTAR (Korea Superconducting Tokamak Advanced Research) tokamak generates neutrons with a peak yield of 2.5 x 10(16) s(-1) through a pulse operation of 300 s. Since the structure material of the tokamak is irradiated with neutrons, this environment will restrict work around and inside the tokamak from a radiation protection physics point of view after shutdown. Identification of neutron-produced radionuclides and evaluation of absorbed dose in the structure material are needed to develop a guiding principle for radiation protection. The activation level was evaluated by MCNP4C2 and an inventory code, FISPACT. The absorbed dose in the working area decreased by 4.26 x 10(-4) mrem h(-1) in the inner vessel 1.5 d after shutdown. Furthermore, tritium strongly contributes to the contamination in the graphite tile. The amount of tritium produced by neutrons was 3.03 x 10(6) Bq kg(-1) in the carbon graphite of a plasma-facing wall.

Computer Simulation↗
PubMed1986

The dihydroorotase domain of the multifunctional protein CAD. Subunit structure, zinc content, and kinetics.

Dihydroorotase (DHOase) catalyzes the third step in eukaryotic de novo pyrimidine biosynthesis. In mammalian cells, this enzyme activity is carried by a large chimeric protein, CAD, that also catalyzes the first two steps in the pathway: glutamine-dependent carbamyl phosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase). Controlled elastase cleavage of CAD released a 44,000 +/- 2,000-dalton proteolytic fragment which catalyzed only the dihydroorotase reaction. We have devised a rapid and simple method for the isolation of the DHO domain from elastase digests. The domain, which was obtained in 36% yield, was found to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing. The domain was also characterized by amino acid analysis and analytical high pressure liquid chromatography peptide mapping. The amino terminus of both the DHO domain and intact CAD was blocked suggesting that this domain is located at the extreme amino terminus of the CAD polypeptide, a result consistent with the suspected juxtaposition of domains as DHO-CPS-ATC. The isoelectric point of the DHO domain was 5.1, while that of the ATC domain was 9.4, so that the ends of the CAD polypeptide are oppositely charged at physiological pH. Immunoblotting with DHO domain-specific antibodies showed that a 47-kDa species was generated in the early stages of controlled proteolysis of CAD. Thus there are two elastase cleavage sites within a 3-kDa connecting region that links the DHO and CPS domains. The domain was shown by atomic absorption spectrophotometry and by isolating a 65Zn-containing DHO domain from mammalian cells grown in the presence of the radionuclide to contain 1 g eq of tightly bound zinc in each polypeptide chain. Zinc was not found in any other CAD domain. Chelating agents inhibit dihydroorotase activity of the isolated domain supporting the conclusion, based on studies of intact CAD by others, that zinc participates in catalysis. At moderate protein concentrations the DHO domain was a 88,000 dimer with a Stokes radius of 37.6 A, a S20,w = 5.1 X 10(-13) s, a diffusion coefficient of 3.17 X 10(-7) cm2 s-1, and a frictional ratio of 1.26. On dilution the dimer dissociated and was in rapid concentration-dependent equilibrium with a 43,500 monomer. The hydrodynamic parameters of the monomer have also been estimated (Stokes radius of 29.8 A, D20,w = 4.11 X 10(-7) cm2 s-1, and f/f0 1.21).(ABSTRACT TRUNCATED AT 400 WORDS)

Amidohydrolases↗
PubMed1994

[Quantitative assessment of scattered photons considering skull bone in brain SPECT].

A Monte Carlo simulation was performed to estimate scattered photons generated in skull bone in brain SPECT. In the simulation, we used cylindrical phantoms which consisted of water and calcium. We calculated energy spectra of planar images and the scatter fractions, which were defined by the ratio of the scattered photons to primary photons, within the energy windows of 20% centered at the photopeak energy. For radionuclides [99mTc (141 keV), 123I (159 keV)], we changed the following parameters: the thickness of the calcium layer (0.0, 0.5, 1.0, 1.5 cm) and its density (1.55, 1.70, 1.85 g/cm3). The results showed that the shape of the energy spectra depended on the photon energy, the thickness of skull and its density. Consequently, the scatter fractions within the energy windows varied from 0.23 to 0.25 (without skull) and from 0.28 to 0.42 (with skull).

Brain↗
PubMed1984

Quantitation of myocardial infarct size from thallium-201 images: validation of a new approach in an experimental model.

A new computer-based method has been developed to quantitate myocardial infarct size from the size of the regional thallium-201 deficit. The operator outlines the left ventricular myocardial activity with an ellipse. The program then plots the background-corrected activities of the highest mean value in a 3 pixel myocardial band perpendicular to and within the ellipse. The approach uses a new interpolative background correction. To determine the accuracy of this approach in assessing regional thallium deficit size, acute myocardial infarction was produced in six dogs by 24 hour occlusion of the proximal left anterior descending coronary artery. Infarct size was assessed from planar thallium images of the dog heart in three views, each with the chest opened and closed and with the heart excised and placed in a cradle. Before removal of the heart, triphenyltetrazolium chloride was infused to delineate normal from infarct tissue. Transverse slices of left ventricle were made and thallium images of the slices acquired. Infarct size delineated by triphenyltetrazolium chloride staining was expressed as a percent of the total left ventricular slice surface area (planimetric infarct size). Infarct size from whole heart and left ventricular slice thallium images was expressed as a percent of the total length of the left ventricular perimeter (perimetric infarct size). This was determined from points below a certain percent of normalized peak thallium activity in the computer-generated thallium activity curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons, sensory neuropeptides, and prostaglandins.

The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.

Analysis of Variance↗
PubMed2003

Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts.

Although radioimmunotherapy with radiolabeled intact monoclonal antibodies has demonstrated efficacy in the treatment of lymphoma, it provides low tumor-to-normal-tissue radionuclide target ratios and unwanted prolonged radiation exposure to the bone marrow. To overcome these obstacles, the administration of the radionuclide was separated from that of the antibody by using an anti-IL-2 receptor alpha antibody single chain Fv-streptavidin fusion protein, followed by radiolabeled biotin to treat lymphoma or leukemia xenografted mice. This Pretarget approach provided extremely rapid and effective tumor targeting, permitting the use of short-lived alpha-emitting radionuclides. With the beta-emitter (90)Y, all of the 10 lymphoma-xenografted mice were cured. With the alpha-emitter (213)Bi, significant efficacy was obtained in treating leukemic mice, and, furthermore, when combined with immunotherapy, 7 of 10 leukemic mice were cured. Thus, Pretarget radioimmunotherapy is very promising and could represent the next generation in the treatment of lymphoma and leukemia.

Animals↗
PubMed1984

Visualization of the liver, gallbladder, and intestine on bone scintigraphy.

Images of the liver, gallbladder, and/or intestine were visualized on bone scans on several occasions. Radiopharmaceutical quality control data, including molybdenum-99 and aluminum ion content in the Tc-99m eluate, free unbound Tc-99m, and hydrolyzed reduced Tc-99m in the labeled MDP, were all satisfactory. A minor defect in the quality of the Tc-99m generator was considered to be the probable cause of the unusual localization of the bone imaging agent.

Bone and Bones↗
PubMed2001

Emission tuned-aperture computed tomography: a novel approach to scintimammography.

UNLABELLED: Emission tuned-aperture computed tomography (ETACT) is a new approach to acquiring and processing scintimammography data. A gamma camera with a pinhole collimator is used to acquire projections of the radionuclide distribution within the breast. Fiducial markers are used to reconstruct these projections into tomographic slices. Simulation and phantom experiments were performed to evaluate the potential of the ETACT method. METHODS: In the simulation study, a hemispheric object of 15 cm in diameter was constructed to model a breast. A ray-tracing technique was used to generate ideal projections. These were blurred and noise was added to create images that resemble scintigraphic images. Tumor size, pinhole size, and target-to-nontarget radioactivity ratios (TNTs) were varied. The simulated projections were reconstructed into slices, and contrast and contrast-to-noise ratios were calculated to evaluate the effect of pinhole size. These results were compared with a simulated planar acquisition of the same object. A preliminary phantom evaluation was performed using an 8-mm "tumor" with a 10:1 TNT to validate the simulation results. RESULTS: A 3-mm pinhole was shown by the simulation study to be the optimal size. The ETACT images consistently yielded higher contrast than simulated planar images. The phantom study validated the simulation results and showed the feasibility of ETACT in a simulated clinical environment. CONCLUSION: ETACT is shown to be useful for imaging tumors <1 cm in diameter. Because ETACT requires only a gamma camera with a pinhole collimator, it has the potential to be applied in any hospital in a simple, flexible, and practical manner.

Breast↗
PubMedDate not supplied

[137Cs distribution and accumulation in the tissues of cultivated fungi (Pleurotus ostreatus)].

The authors examined 137Cs accumulation and distribution in different structures and tissues of Pleurotus ostreatus cultivated under laboratory conditions. The fungi were shown to concentrate 137Cs. A higher concentrations of the radionuclides in the fungi compared to their substrate is manifested at the first stages of the fruit body formation, the maximum content of 137Cs is accumulated by fungi in the middle of bearing stage. The fungus tissues are different by their accumulative capacity as follows (ascending range): central, more dense part of the stipe < stipe < mycelium < cap < generative tissues. 137Cs accumulation in the fruit bodies depends also on the fungus size and age.

Cesium Radioisotopes↗
PubMed2006

Tumor imaging using a picomolar affinity HER2 binding affibody molecule.

The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, Z(HER2:342) showed a >2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging.

Amino Acid Sequence↗
PubMed1988

Non-invasive measurement of pulmonary arterial pressure: II. A radionuclide method.

Pulmonary artery pulse pressure (PP) and diastolic pressure (Pd) may be obtained by applying a haemodynamic model of blood flow kinetics and wall mechanics to the pulmonary artery: Pp = rho(ws/(Ss/Sd-1))2log(Ss/Sd)-1/2 rho w2s Pd = (Sd/Ss)1/2Pp where rho is blood density, ws is peak ejection velocity, and Ss and Sd are peak maximal and end diastolic cross-sectional areas of the main pulmonary artery. The different parameters of the equations were measured from radionuclide first pass and equilibrium studies. Radionuclide first pass studies were performed in 24 patients with intravenous injection of 20 mCi of 99Tcm red blood cells with a gamma camera in a 20 degrees right anterior oblique position: data were collected in list mode, i.e. a continuous sequence of spatial and temporal coordinates of each photon. Pulmonary arterial pressure was recorded simultaneously with a microtip catheter during the first pass study. Gated first pass images of the right side of the heart were reconstructed, regions of interest drawn over the right ventricle and the main pulmonary artery (MPA) and time-activity curves generated. Peak systolic (Cs) and end diastolic (Cd) counts obtained from the MPA curve were proportional to the cross sections Ss and Sd of the MPA and Ss/Sd = Cs/Cd. The diameter (D) of the pulmonary artery was calculated as the distance between the two zeros of the second derivative of a cross-sectional profile. The averaged cross-sectional area was S = pi D2/4. ECG gated blood pool studies were performed in a LAO 40 degrees position when the tracer was at equilibrium; they were processed automatically and the right ventricular end diastolic counts (EDC) converted into volume (EDV) using an aortic volume/count ratio. Right ventricular peak ejection rate (PER) was obtained from the RV time-activity curve and the instantaneous peak ejection velocity was calculated, ws = PER X EDV/S X EDC. PP and Pd were calculated in mmHg and the radionuclide method yielded pressure values that correlated reasonably with catheterisation values: PP(rad) = 0.99 PP(cath)-0.55, r = 0.84 and Pd(rad) = 0.67 Pd(cath) + 4.91, r = 0.74. We conclude that radionuclide techniques can provide a non-invasive method based on a haemodynamic model for measuring pulmonary arterial pressure.

Adult↗
PubMed2003

A model-based method for the prediction of whole-body absorbed dose and bone marrow toxicity for 186Re-HEDP treatment of skeletal metastases from prostate cancer.

In high-activity rhenium-186 hydroxyethylidene diphosphonate ((186)Re-HEDP) treatment of bone metastatic disease from prostate cancer the dose-limiting factor is haematological toxicity. In this study, we examined the correlation of the injected activity and the whole-body absorbed dose with treatment toxicity and response. Since the best response is likely to be related to the maximum possible injected activity limited by the whole-body absorbed dose, the relationship between pre-therapy biochemical and physiological parameters and the whole-body absorbed dose was studied to derive an algorithm to predict the whole-body absorbed dose prior to injection of the radionuclide. The whole-body retention of radioactivity was measured at several time points after injection in a cohort of patients receiving activities ranging between 2,468 MBq and 5,497 MBq. The whole-body absorbed dose was calculated by fitting a sequential series of exponential phases to the whole-body time-activity data and by integrating this fit over time to obtain the whole-body cumulated activity. This was then converted to absorbed dose using the Medical Internal Radiation Dose (MIRD) committee methodology. Treatment toxicity was estimated by the relative decrease in white cell (WC) and platelet (Plt) counts after the injection of the radionuclide, and by their absolute nadir values. The criterion for a treatment response was a 50% or greater decrease in prostate-specific antigen (PSA) value lasting for 4 weeks. Alkaline phosphatase (AlkPh), chromium-51 ethylene diamine tetra-acetate ((51)Cr-EDTA) clearance rate and weight were measured before injection of the radionuclide. The whole-body absorbed dose showed a significant correlation with WC and Plt toxicity ( P=0.005 and 0.003 for the relative decrease and P=0.006 and 0.003 for the nadir values of WC and Plt counts respectively) in a multivariate analysis which included injected activity, whole-body absorbed dose, pre-treatment WC and Plt baseline counts, PSA and AlkPh values, and the pre-treatment Soloway score. The injected activity did not show any correlation with WC or Plt toxicity, but it did correlate with PSA response ( P=0.005). These results suggest that the administration of higher activities would be likely to generate a better response, but that the quantity of activity that can be administered is limited by the whole-body absorbed dose. We have derived and evaluated a model that estimates the whole-body absorbed dose on an individual patient basis prior to injection. This model uses the level of injected activity and pre-injection measurements of AlkPh, weight and (51)Cr-EDTA clearance. It gave good estimates of the whole-body absorbed dose, with an average difference between predicted and measured values of 15%. Furthermore, the whole-body absorbed dose predicted using this algorithm correlated with treatment toxicity. It could therefore be used to administer levels of activity on a patient-specific basis, which would help in the optimisation of targeted radionuclide therapy. We believe that algorithms of this kind, which use pre-injection biochemical and physiological measurements, could assist in the design of escalation trials based on a toxicity-limiting whole-body absorbed dose, rather than using the more conventional activity escalation approach.

Body Burden↗