Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals.

It is widely recognized that radiopharmaceuticals are generally distributed nonuniformly in tissues. Such nonuniformities are observed over the entire range of spatial levels, ranging from organ to subcellular levels. The implications of nonuniform distributions of radioactivity for dosimetry, and ultimately for the biologic response of tissues containing radioactivity, have been investigated extensively. However, there is a paucity of experimental data on the distribution of cellular activity within a population of cells. In the present study, the distribution of activity per cell is experimentally determined and its implications for predicting biologic response are examined. METHODS: Chinese hamster V79 cells were exposed to different concentrations of (210)Po-citrate. The radiolabeled cells were washed, seeded into culture dishes or glass slides, covered with photographic emulsion, and stored in an opaque container. Subsequently, the emulsion was developed, thereby resulting in observable alpha-particle tracks that were scored. RESULTS: The distribution of activity per cell was found to be well described by a log normal distribution function. Theoretic modeling of cell survival as a function of mean activity per cell showed that survival curves differed substantially when the activity per cell was log normally distributed versus when it was assumed conventionally that every cell in the population contained the mean activity. CONCLUSION: The present study provides experimental evidence of log normal cellular uptake of radioactivity. Theoretic calculations show that a log normal distribution of cellular activity can have a substantial impact on modeling the biologic response of cell populations.     

Lognormal distribution of cellular uptake of radioactivity: statistical analysis of alpha-particle track autoradiography.

Recently, the distribution of radioactivity among a population of cells labeled with 210Po was shown to be well described by a lognormal (LN) distribution function (J Nucl Med. 2006;47:1049-1058) with the aid of autoradiography. To ascertain the influence of Poisson statistics on the interpretation of the autoradiographic data, the present work reports on a detailed statistical analysis of these earlier data. METHODS: The measured distributions of alpha-particle tracks per cell were subjected to statistical tests with Poisson, LN, and Poisson-lognormal (P-LN) models. RESULTS: The LN distribution function best describes the distribution of radioactivity among cell populations exposed to 0.52 and 3.8 kBq/mL of 210Po-citrate. When cells were exposed to 67 kBq/mL, the P-LN distribution function gave a better fit; however, the underlying activity distribution remained lognormal. CONCLUSION: The present analysis generally provides further support for the use of LN distributions to describe the cellular uptake of radioactivity. Care should be exercised when analyzing autoradiographic data on activity distributions to ensure that Poisson processes do not distort the underlying LN distribution.     

'Early' thyroid 123I uptake: correction for extrathyroidal neck radioactivity.

Should one correct for extrathyroidal neck radioactivity ('neck background') when interpreting perchlorate discharge test results? A new background correction method was developed using a linear probe. 123I produces photon peaks at two energy levels: 159 keV (gamma-rays) and 28 keV (X-rays), with an attenuation of 15 and 35% per cm water, respectively. If one fixes the position of the subject's neck, radiation from thyroid 123I produces an X/gamma detection ratio (alpha) which is constant and, due to the anterior localization of the thyroid, higher than the ratio (beta) produced by extrathyroidal 123I. These two ratios can be determined in vivo and used to calculate background-corrected and depth-corrected thyroid uptake. In simulation experiments our method was effective so long as the 'gland' was situated close enough to the 'neck' surface for the difference (alpha-beta) to be less than 0.19. Perchlorate discharge tests were performed in five euthyroid subjects who were pretreated with methimazole. The difference (alpha-beta) ranged from 0.27 to 0.36. Uncorrected, the mean discharge was 57% (range 47-66); corrected, it was 92% (range 88-94). In 15 hyperthyroid Graves' patients, with goitres varying from 13 to 63 ml, alpha-beta ranged from 0.22 to 0.40 and was unrelated to goitre size. The contribution of neck background is quantitatively important, especially when thyroid uptake is low; our new method corrects for it, even with large goitres.     

Automated, high-resolution cellular retention and uptake studies in vitro.

This report describes an automated method for the measurements of cellular retention and uptake of radiolabeled proteins interacting with cell-surface receptors on intact cancer cells. A complete uptake and retention measurement was performed in one cell dish using a rotating radioimmunoassay (RIA) principle. Compared to common manual measurements, rotating RIA saved both labor time and reagents and provided real-time binding traces with superior time-resolution. The rotating RIA retention profiles for different interactions agreed with retention times reported in the literature.     

Knee effusion: normal distribution of fluid.

Although visualization of articular fluid on MR images of the knee is common, no specific MR criteria that enable assessment of the quantity of the effusion have been established. We performed MR of three cadaveric knee specimens after the instillation of increasingly large volumes of fluid and studied the distribution of the fluid. When 4 ml of fluid was injected, the anteroposterior diameter of the suprapatellar recess was 4 mm on midline sagittal MR images and 10.0-12.5 mm on lateral sagittal MR images, corresponding to the usual routine radiographic criteria for a knee effusion.     

Underground measurements of radioactivity.

The exceptional sensitivity of gamma-ray spectrometry in underground laboratories has increasing application because of the important science and technology that it allows to be studied. Early work focused on rare fundamental phenomena, e.g. double beta decay, but a growing number of underground measurements is being performed in fields such as environmental monitoring, surveillance of nuclear activities, benchmarking of other physical techniques and materials selection for equipment which require materials with extremely low levels of radioactivity. This report describes the state of the art in underground gamma-ray spectrometry. Backgrounds of HPGe-detectors at various underground laboratories are presented and compared. Improved techniques and detectors are described and needs of deep underground facilities for higher sensitivity measurements are discussed.     

Environmental radioactivity monitoring in Portugal.

Environmental radioactivity monitoring in Portugal is a nationwide programme that consists of two complementary (sparse and dense) sampling networks established following the EURATOM recommendations [2000/473/EURATOM-Commission Recommendation of 8 June 2000, Official Journal of the European Commission, no. 191, 27 June 2000]. This paper describes the aim of the monitoring programme, how it was implemented, the sampling locations, the type of samples, the analytical and measurement methods and the quality control programmes. Some representative results are also discussed. Based on the monitoring data it can be concluded that the Portuguese population has not been exposed to radioactivity levels that require any radiological protection measures.     

Thermodynamic stability of radioactivity standard solutions.

Optimal thermodynamic stability conditions must prevail when radioactivity standard solutions are prepared. These conditions are studied, they relate to: * The nature of the radioactive ion, which makes it possible to establish the pH of the solubilization medium at a given concentration, * The carrier concentration, which is determined by considering the radionuclide production method and the prior concentration in the original solution from the supplier, * The most stable oxidation state of the radioactive ion and of the carrier ion, which must be considered at the pH established by the solubilization medium. A procedure for all the glassware used in preparation has been implemented.     

Dynamic hepatobiliary SPECT: a method for tomography of a changing radioactivity distribution

Dynamic single photon emission computed tomography (SPECT) of a changing radioactivity distribution can be performed with a rotating scintillation camera by acquiring several 360 degree studies and generating a new 360 degree study for which the acquisition time for every image is shifted to a single selected time. Following suppression of gallbladder filling with a fatty meal, dynamic SPECT of the hepatobiliary system was carried out by acquiring two successive studies with each head of a dual-headed camera within a 35-min period following injection of technetium-99m DISIDA. Each of the four acquired studies consisted of 60 images acquired at 6 degree intervals, spanning 360 degrees. Time-shifted studies, each consisting of 60 images over 360 degrees, were generated for times 9, 17, and 26 min postinjection. Transverse, sagittal, and coronal images were generated for each study. These images were artifact-free and demonstrated physiologic shifting of the radioactivity distribution over time. When gallbladder filling was not suppressed gross artifacts were obtained. This procedure permits examination of regional liver function and provides improved visualization of the biliary tree.     

Natural radioactivity in Algerian building materials.

Samples of natural and manufactured building materials collected from Algiers have been analysed for 226Ra, 232Th and 40K using a high-resolution HPGe gamma-spectrometry system. The specific concentrations for 226Ra, 232Th and 40K, from the selected building materials, ranged from (12-65 Bq kg(-1)), (7-51 B qkg(-1)) and (36-675 Bq kg(-1)), respectively. The measured activity concentrations for these natural radionuclides were compared with the reported data of other countries and with the world average activity of soil. Radium-equivalent activities were calculated for the measured samples to assess the radiation hazards arising from using those materials in the construction of dwellings. All building materials showed Ra(eq) activities lower than the limit set in the OECD report (370 Bq kg(-1)), equivalent to external gamma-dose of 1.5 mSv yr(-1).     

Poor technetium-99m-DMSA renal uptake with near normal technetium-99m-DTPA uptake caused by tubulointerstitial renal disease.

We present a patient with tubulointerstitial renal disease and poor renal 99mTc-DMSA uptake. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. In this case, 99mTc-DMSA uptake did not correlate with "global renal function," but rather with the functioning tubular mass.     

Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome.

PURPOSE: Previous studies in chronic fatigue syndrome (CFS) have reported reductions in maximal oxygen uptake (VO(2max)), yet often the testing procedures have not followed accepted guidelines, and gender data have been pooled. The present study was undertaken to reevaluate exercise capacity in CFS patients by using "gold standard" maximal exercise testing methodology and stratifying results on a gender basis. METHODS: Sixteen male and 17 female CFS patients and their gender-, age-, and mass-matched sedentary controls performed incremental exercise to volitional exhaustion on a stationary cycle ergometer while selected cardiorespiratory and metabolic variables were measured. RESULTS: VO(2max) in male CFS patients was not different from control values (CFS: 40.5 +/- 6.7; controls: 43.3 +/- 8.6; mL x kg(-1) x min(-1)) and was 96.3 +/- 17.9% of the age-predicted value, indicating no functional aerobic impairment (3.7 +/- 17.9%). In female CFS patients, VO(2max) was lower than control values (CFS: 30.0 +/- 4.7; controls: 34.2 +/- 5.6; mL x kg(-1) x min(-1), P = 0.002), but controls were higher than the age-predicted value (112.6 +/- 15.4%, P = 0.008) whereas the CFS patients were 101.2 +/- 20.4%, indicating no functional aerobic impairment (-1.2 +/- 20.4%). Maximal heart rate (HR(max)) in male CFS patients was lower than their matched controls (CFS: 184 +/- 10; controls: 192 +/- 12; beats x min(-1); P = 0.016) but was 99.1 +/- 5.5% of their age-predicted value. In female CFS patients, HR(max) was not different from controls (CFS: 183 +/- 11; controls: 186 +/- 10; beats x min(-1)) and was 98.9 +/- 5.1% of the age-predicted value. The VO(2) at the lactate threshold (LT) in each gender group, whether expressed in mL x kg(-1) x min(-1) or as a percentage of VO(2max), was not different between CFS patients and controls. CONCLUSIONS: In contrast to most previous reports, the present study found that VO(2max), HR(max), and the LT in CFS patients of both genders were not different from the values expected in healthy sedentary individuals of a similar age.     

Expression of the hemochromatosis (HFE) gene modulates the cellular uptake of 67Ga.

Recent studies have revealed that the wild-type hemochromatosis protein (HFE) interacts with the transferrin receptor (TfR) and modulates TfR-mediated iron uptake by cells. Because of similarities in the transport of gallium and iron and the use of (67)Ga scanning in lymphoid malignancies, we examined the effect of HFE expression on (67)Ga uptake. METHODS: (67)Ga and (59)Fe uptakes were measured in HeLa cells transfected with a FLAG-tagged wild-type HFE (fHFE) gene under control of a tetracycline-repressible promoter. fHFE and TfR protein levels were measured by Western blotting; cellular transferrin (Tf) binding sites were measured by (125)I-Tf binding assay. RESULTS: Induction of fHFE expression produced an increase in TfR protein that was accompanied by a decrease, rather than an increase, in cellular (67)Ga and (59)Fe uptake. The difference in (67)Ga uptake between fHFE-expressing and fHFE-nonexpressing cells was markedly increased in the presence of Tf. Although fHFE expression produced an increase in cellular TfR protein, cell surface and intracellular Tf binding sites were actually decreased in these cells. CONCLUSION: Our studies suggest that expression of wild-type HFE in cells produces a decrease in (67)Ga uptake due to a reduction in available Tf binding sites for (67)Ga-Tf on the TfR. These results imply that (67)Ga uptake by cells with wild-type HFE may differ from cells with the HFE C282Y mutation.