P.C. Minnaar

Kinetics, Distribution and Sites of Destruction of 111Indium‐labelled Human Platelets

The survival, tissue distribution and fate of 111In‐oxine labelled autologous platelets in six normal humans were studied with serial blood sampling, scintillation camera and computer‐assisted imaging, whole body profile scanning, and rectilinear scanning. 111In‐platelets recovery in the circulation was 72±16% and survival was 216±17 h. Platelet survival curves fitted a linear function best. Initially platelets pooled rapidly in the spleen as a single exponential function, and at 90 min 26% of the injected 111In was located in this organ. Early hepatic uptake was also significant and at 90 min constituted 16% of total body 111In‐activity. As labelled platelets disappeared from the circulation there was a threefold increase of radioactivity in the liver to reach 39% of whole body activity at 216 h. Radioactivity also increased significantly in the spleen (33±3% at 216 h). There was significant residual radioactivity in the thoracic and lower abdominal regions at 216 h, suggesting that platelets are also sequestered in the bone marrow. Radioactivity in the lower limbs almost disappeared with time (0±7% at 216 h), indicating that utilization of platelets in the peripheral vasculature is not marked in normal subjects.

A computer program in compiled basic for the IBM personal computer to calculate the mean platelet survival time with the multiple-hit and weighted mean methods

We developed an easy-to-operate computer program for the IBM personal computer to calculate, display and store in a database platelet kinetic data determined by analysis of the rate of clearance of radiolabeled blood platelets from the circulation. This was done by curve fitting using the weighted mean method and multiple-hit model. These models are complementary and calculating the mean platelet survival time with both is recommended. Improvement of the weighted mean method was investigated. The optimized weighting and fitting the exponential function with the Marquardt non-linear least squares method improved the weighted mean method. The weighted mean and multiple-hit models fit the survival curve data equally well. The calculation of the mean platelet survival time with the weighted mean method was very fast. The duration of calculation with the multiple-hit model could take up to 2 minutes. Calculation of the mean platelet survival time using both models has the advantage that conditions when calculation of the mean platelet survival time would be invalid, can be detected. The computer program will promote the valid comparison of results obtained at different institutions.

Radiation dose from human platelets labelled with indium 111

The biological distribution of 111In-labelled platelets in normal subjects was determined by whole-body counting and scintillation-camera computer-assisted imaging. Using these data, organ radiation dose was quantitated. The highest radiation dose of 7.4 mGy/MBq (27.4 rad/mCi) was received by the spleen and 0.97 mGy/MBq (3.6 rad/mCi) by the liver. While body radiation dose was 0.25 mGy/MBq (0.9 rad/mCi). The gonad radiation dose of males was 0.14 mGy/MBq (0.5 rad/mCi) and that of females 0.22 mGy/MBq (0.8 rad/mCi). These estimates indicate that radiation doses received from 8.6 MBq of 111In-labelled platelets are well within acceptable limits, and that 111In is a safe labelling agent for the study of platelet kinetics.

An evaluation of four methods of 111In planar image quantification

The accurate quantification of the in vivo distribution of 111In labeled platelets, other cells, and proteins with a scintillation camera is important in clinical and experimental medicine. Planar techniques of image quantification were therefore evaluated with the aim of improving on the accuracy, and simplifying the techniques currently in use. The attenuation of the 172- and 247-keV photons of 111In, singly and in combination, was determined for varying diameter flat sources (3.4 to 16.9 cm). The influence of region of interest (ROI) selection on the shape of the attenuation curves was also determined for five different ROIs. Defining the attenuation curves mathematically generated parameters of fit for three approaches to in vivo quantification, namely: a single exponential geometric mean approach that takes into account source size, depth-dependent, and depth-independent buildup factor approaches to account for the contribution of scatter. The accuracy of these techniques was ascertained and compared to the classical geometric mean method. This was done in a waxen phantom of a human thorax with a hollow liver and spleen. The results indicated that the depth-independent buildup factor is the best method; the error for quantification in the spleen was 0.8% +/- 2.2%. The classical geometric mean approach gave a corresponding error of 43.3% +/- 3.4%. Since the attenuation of the two energies of 111In differ, their ratio changes with depth. This phenomenon was investigated with the goal of determining whether the depth of an object can be estimated from one set of planar images. This was not successful.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of the ‘collection injury’ on the survival and distribution of Indium- 111 -labelled canine platelets

Summary. The extent of the ‘collection injury’ sustained by platelets during labelling with In‐lll‐oxine was investigated in three matched pairs of beagle dogs. The influence of the procedure on the survival, kinetics, in vivo distribution and fate of the labelled platelets was determined by serial blood sampling and quantitative computerized scintillation camera studies. Injured labelled platelets were removed in the matched dog acting, as a biological filter. The survival, distribution and fate of the ‘filtered’ and ‘unfiltered’ platelets were compared. The mean platelet lifespan of the ‘filtered’ and ‘unfiltered’ platelets did not differ significantly, but the shape of the survival curve of the filtered platelets fitted a linear function more closely than that of the unfiltered platelets. Radioactivity in the different organs and regions was serially quantitated and expressed as a percentage of whole body radioactivity. Splenic and hepatic radioactivity of filtered and unfiltered platelets did not differ significantly at equilibrium or at the end of platelet lifespan. It is concluded that the currently employed isolation and labelling techniques for platelets are suitable for quantitative in vivo studies with a computerized scintillation camera system. The shape of platelet survival curves should, however, be interpreted with some caution as it may be influenced by these procedures.

Investigation into the effect of Fenoterol on mucociliary clearance in patients with chronic bronchitis

We investigated the effects of Fenoterol, a selective β2 adrenoceptor stimulant, on mucociliary clearance in 12 patients with chronic bronchitis. Mucociliary clearance was measured with a scintillation camera after inhalation of a 99mTc labelled aerosol. Fenoterol was administered one h after acquisition commenced and imaging was maintained for a further two h. Three regions of interest (ROI) were selected over each lung to generate time activity curves. Corrections for decay, alveolar deposition (using 24 h image), cough and movement of activity through each ROI were carried out. An exponential function was fitted to the clearance curves to determine clearance rates. The increase in percentage clearance after Fenoterol administration for the left and right whole lung ROI was 35% and 36% per h respectively (P=0.006 and 0.020). Fenoterol enhances cilial clearance in chronic bronchitis patients.

Evaluation of Models to Determine Platelet Life Span and Survival Curve Shape

The value of radionuclide platelet survival studies to delineate the mechanisms of thrombocytopenia and factors contributing to it has been proven (1), and the effect of various diseases and therapies on platelet survival may be evaluated by the same technique. The recent introduction of 111In-oxine as a cellular label allowing in vivo imaging of platelet distribution, has renewed interest in platelet kinetic studies (2,3).

Radionuclide cholescintigraphic imaging: An evaluation of several 99mTc labelled hepatobiliary radiopharmaceuticals

Recently, much interest has been shown in the development of 99mTc labelled cholescintigraphic agents for imaging the hepatobiliary tract. In this study six cholescintigraphic agents were compared in rabbits with respect to transit efficiency through the liver and the halftime on the washout portion of the liver time-activity curve. The agents compared were p-butyl-IDA (PBIDA), diisopropyl-IDA (DISIDA), two mebrofenin (MBF) agents and two pyridoxylaminates (PDA). Best transit efficiencies were obtained with MBF (34.1 and 31.2%) followed by PDA (27.7 and 24.9%) while DISIDA (23%) and PBIDA (19.3%) were the lowest. The same phenomenon was observed regarding the washout halftime, with MBF the most rapid (6.3 and 5.9 min), PDA more prolonged (10.1 and 12.0 min) and DISIDA and PBIDA the slowest (23.0 and 23.2 min). This study confirms the difference in physiological behaviour of the various cholescintigraphic agents and shows identical flow patterns for locally produced and imported compounds.

Evaluation of (o)-[77Br]bromohippuran as renal tubular function agent.

(o)-[77Br]bromohippuran (BHIP) was developed as renal tubular function agent due to its favourable chemical and physical properties and compared to (o)-[131I]iodohippuran (IHIP). Renograms obtained from baboons were compared and absorbed radiation dose calculations performed. Although BHIP showed a delayed kidney uptake and washout pattern, good kidney clearance of the radionuclide was obtained after 30 min. Radiation dose values for BHIP were markedly lower than for IHIP indicating that larger activities of BHIP could be administered to increase counting statistics. BHIP imaging in normal volunteers did however not substantiate the favourable behaviour obtained in the primate.

Determination of right ventricular ejection fraction utilising a radionuclide washout technique

A radionuclide washout technique (WO), for calculation of the right ventricular ejection fraction (RVEF) which is independent of the exact position of the right ventricular region of interest was evaluated and results compared with first pass (FP) and equilibrium gated blood pool (GBP) values. Regression analysis between RVEF values of 24 patients obtained from FP and WO yielded a correlation coefficient (r) of 0.89, while a slightly poorer correlation coefficient was obtained when FP and GBP were compared (r=0.79) and between WO and GBP (r=0.71). No significant difference between RVEF values calculated from the three techniques was found (P<0.05) on inter- and intraobserver level. The radionuclide washout technique yields an accurate determination of RVEF without the necessity of outlining the RV accurately.