Richard C. Reba

Effect of phenobarbital on 99mTc-IDA scintigraphy in the evaluation of neonatal jaundice

Hepatobiliary scintigraphy with 99mTc-IDA derivatives was used to evaluate 40 neonates with mixed jaundice. Fourteen patients proved to have biliary atresia. The remaining 26 patients had intrahepatic cholestasis with patent extrahepatic ducts. Sixteen of the 40 patients underwent examinations without phenobarbital stimulation. Sixteen patients had two examinations, one before and one after 3-7 days of phenobarbital therapy. The remaining 8 patients had their initial examinations after phenobarbital therapy. The results of this study show that administration of phenobarbital in a dose of 5 mg/kg/day for at least 5 days prior to the examination enhances and accelerates biliary excretion of IDA compounds and thereby significantly increases the accuracy of 99mTc-IDA scintigraphy in differentiating extrahepatic biliary atresia from neonatal hepatitis. Its routine use in the evaluation of neonatal jaundice is therefore highly recommended.

Extra-osseous localization of 99Tcm-Sn pyrophosphate

99Tcm-Sn pyrophosphate bone scans of 250 patients referred for skeletal metastatic survey were analysed to determine the frequency of abnormal extra-osseous localization and the various pathological causes. Twenty-six patients demonstrated abnormal extra-osseous concentration. There were three false positives. Sixty-five per cent of the extra-osseous lesions concentrating pyrophosphate were malignant (carcinoma of lung and breast, metastatic hepatic carcinoma, chondrosarcoma) and the remainder were benign lesions, e.g. sarcoidosis, soft-tissue calcification, post-surgical and irradiation sites. An incidental finding was the unusual frequency of accumulation of pyrophosphate in various joints, especially the knees and shoulders in asymptomatic patients above 70 years of age.

Synthesis, plasma clearance, and in vitro stability of protein containing a conjugated indium-111 chelate

A new bifunctional chelating agent, N′-(p-diazoniumbenzyl)-N,N N″,N″-diethylenetri-aminetetraacetic acid (DTTA) was synthesized. The compound as coupled to methyl p-hydroxybenzimidate and the resulting azoimidate was attached to lysine residues of monomeric human serum albumin (HSA) via the amidination reaction. Blood clearnace of111In-labelled DTTA conjugated to HSA (AAHSA) in rabbits was biphasic. The first phase has a clearance indistinguishable from that of125I-labeled HSA. During the second phase, the111In-labeled AAHSA was cleared more rapidly so that between 24 hours and 48 hours the percent of the injected dose of111In-labeled AAHSA in the blood was significantly lower than that of125I-labeled HSA. Highly conjugated111In-labeled AAHSA (0.9 DTTA/HSA) showed accelerated clearance at 24 and 48 hours compared to lightly conjugated protein (<0.9 DTTA/HSA). As a result we postulate that the level of conjugation is the critical parameter controlling the blood clearance.

Accuracy of in vivo neuroreceptor quantification by PET and review of steady-state, transient, double injection, and equilibrium models

The accuracy of in vivo dopamine D2 receptor quantification by positron emission tomography (PET) was determined for several models by means of singular-value decomposition, and some of the model assumptions were reviewed. These include steady-state, transient, double injection, and equilibrium approaches. All four modes are augmented by including a realistic kinetic interaction of the radioligand with the striatal serotonin S2 receptor. When a set of parameters derived specifically with reference to the equilibrium model was applied, it was found that a reversible radioligand used in conjunction with the equilibrium model permits accurate quantification. However, an assumption of the equilibrium model-that equilibrium is achieved during the time of measurement-is shown to be unsupported by the published experimental data. These results indicate that the equilibrium approach can provide an alternative to the kinetic approaches, but that additional experimental evidence is required to demonstrate the validity of the equilibrium assumption.

Theoretical investigation of the estimation of relative regional neuroreceptor concentration from a single SPECT or PET image

The validity of estimating changes in regional neuroreceptor concentration based upon a single ECT (emission computed tomography) image is examined to determine whether an image can be acquired at a time when changes in the observed regional radioactivity are much more sensitive to changes in receptor concentration than to changes in radioligand delivery. These sensitivities are defined as the normalized partial derivatives of the regional radioactivity signal (S) with respect to the total receptor (R(t)) and with respect to radioligand delivery (k(1)). Using computer simulations, it is found that ( partial differentials/ partial differentialR(t))/( S/R(t)) can be less than unity (receptor hyposensitivity), approximately equal to unity, or significantly greater than unity (receptor hypersensitivity). It is possible to find classes of parameter sets under which the receptor sensitivity is close to unity and the delivery sensitivity is of much lower magnitude. The results indicate that if the parameters for a given radioligand-neuroreceptor system can be established as belonging to one of these classes, then changes in regional neuroreceptor concentration can be estimated based upon a single ECT image.

Quantification of the dopamine D2 receptor in the living human caudate nucleus by PET: comparison of in vivo and in vitro kinetic parameters

It is demonstrated that the set of kinetic parameters (including first-order rate constants for the dissociation of N-methylspiperone (NMSP) from, and second-order rate constants for the association of NMSP to, the dopamine D2 and serotonin S2 receptors of the caudate nucleus) which can be derived from previously reported human caudate PET (positron emission tomographic) data is not uniquely determined, but that multiple sets generate approximately equivalent curve fits. In particular, the set consisting of the in vitro values can generate the PET data. Thus, the in vitro rate constants may apply in vivo.

Theoretical effects of radioligand diffusional gradients and microscopic neuroreceptor distribution in in vivo kinetic studies

A simplified one-dimensional model system was used to test the possibility that physically realistic parameters would lead to the prediction of microscopic heterogeneity of radioligand distribution in the brain and that microscopic heterogeneity of radioligand and neuroreceptor distribution could influence the macroscopically observedin vivo kinetics. The model was represented mathematically by a partial differential equation which is similar to the heat diffusion equation, but with special boundary conditions. The equation was solved analytically under the condition of negligible receptor occupancy by inversion of the Laplace transform and in the more general case of arbitrary receptor occupancy by cubic spline approximation. In simulations with physically reasonable values for rate constants and parameters, we find that significant radioligand gradients can occur. Thus, the level of radioligand in the immediate vicinity of the receptor may be substantially different from the average level in a macroscopically measured region of interest.

Reactivity of amino acids in the azo coupling reaction: I. Dependence of their reactivity on pH

Abstract Azo coupling reactions of N -α-acetylhistidine, N -α-acetyltyrosine, and N -α-acetyllysine with p -methylbenzenediazonium ion were investigated as model reactions to obtain information on the relative reactivity of the histidine, tyrosine, and lysine moieties of protein, separated from structural effects. The azo coupling yields of the amino acids increased as the pH of the reaction medium was increased, indicating that the ractive species are the imidazole anion of histidine, the phenolate anion of tyrosine, and the neutral e-amino group of lysine. It was calculated, based on percentage yields of the azo products, that the imidazole anion is more reactive than the phenolate anion and the e-amino group, respectively.

False Positive 125I fIbrinogen Test

125I fibrinogen test was performed in 20 selected patients who presented with symptoms suggestive of deep venous thrombosis. The incidence of a false positive study was found to be very high: 90%. An increased accumulation of fibrinogen was noted over recent, well-healed surgical incisions, diffuse or focal inflammatory sites, hematoma and also, following a venogram or arthrogram test. The large number of coincidental circumstances that result in an abnormal accumulation of 125I fibrinogen lead us to believe that venogram is the procedure of choice in patients with symptoms simulating thrombophlebitis.

3-D computer simulations of resolution effects of multidetector point focusing SPECT imaging

The authors present an efficient algorithm and the results of its application in simulating the three-dimensional (3-D) projection data resulting from a 3-D distribution of radioactivity. The algorithm was applied to a series of geometrical mathematical phantoms and to a realistic mathematical brain phantom. The authors simulated the projection data from a multidetector single-photon emission computed tomography (SPECT) system with point focusing collimators. The simulated projection data were then reconstructed using the manufacturers software. The objects simulated included simple geometrical solids such as spheres and sheets, as well as the distribution of muscarinic cholinergic receptors in a realistic brain slice. Spheres were chosen as a model for brain structures such as caudate nucleus, thalamus, and cerebellum; sheets were selected as representing lateral cortical gray matter regions. The results of these simulations indicate the existence of significant qualitative and quantitative artifacts in reconstructed human brain images.