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The relative rates of transit through the oesophagus of radiolabelled “Expidet” formulations, tablets, capsules or liquids were measured in 10 healthy supine male and female subjects. The movement of the formulations was followed by gamma scintigraphy. Liquids were observed to clear rapidly in a monoexponential pattern in all subjects. The transit of capsules and tablets in the same subjects was slower and more variable. In two subjects, capsules and tablets were observed to lodge in the lower third of the oesophagus. The “Expidet” formulations cleared from the mouth with several swallows and there was no evidence of oesophageal adhesion. There was no statistically significant difference in total transit time between the formulations.

The gastric emptying of pellets analogous to those used in sustained release preparations has been studied in vivo, using gamma scintigraphy. The results show that under certain conditions, the pellets may not necessarily empty from the stomach in a randomized manner.

SummaryThe sites of deposition and the rates of clearance of a radiolabelled nasal spray solution have been monitored using gamma scintigraphy. In patients with nasal polyposis the rates of clearance were much slower than in normal subjects and in general were not improved following polypectomy. It

The quantitative measurement of regional aerosol deposition in human lungs using two-dimensional (2D) gamma scintigraphy has proven to be useful in therapeutic and diagnostic aerosol studies. The penetration index (PI) has been defined as the ratio of activity in a peripheral lung zone to a central lung zone, but the ability to discriminate between aerosol deposition in the large airways and lung parenchyma is reduced by the fact that the latter overlies the former in the central zone. To overcome this, we used a three-dimensional (3D) technique. Seven healthy subjects inhaled isotonic saline aerosols containing 99mTc-DTPA on two occasions. The droplets had a mass median aerodynamic diameter (MMAD) of either 2.6 or 5.5 microns (with geometric standard deviations [sigma g] of 1.4 and 1.7, respectively). Transmission tomography was performed on each subject to delineate lung boundaries in 2D and 3D. After inhalation, anterior (A) and posterior (P) images were collected and a tomographic study performed. Mid-lung slices were taken from coronal (CC) and transverse (TC) sections. PI was calculated on the 2D images (AP and P) and the 3D slices (CC and TC) using exactly defined regions. The PI values were smaller for the large droplet aerosol (5.5 microns) in all subjects and methods. The relative differences in PI between large and small (2.6 microns) droplet studies (d values) were greater and less variable for the 3D methods (TC, 56.5 +/- 11.4% and CC, 52.4 +/- 12.3%) compared to the 2D methods (P, 25.4 +/- 17.1% and AP, 38.3 +/- 15%; p less than 0.005). We found the 3D methods to be more sensitive for discriminating between aerosol deposition in large and small airways than were the conventional 2D methods.

The spreading of enema solutions has been monitored in four normal subjects using gamma scintigraphy. Two volumes, 50 ml and 200 ml, were administered on separate occasions. Enema dispersion was greater with the 200 ml dose but there was considerable variability. Enema administration and eating stimulated intraluminal colonic motility, but food taken 1 h after enema dosing did not affect spreading. Aboral movement of the colon contents appears to inhibit dispersion. It is concluded that 100 ml is the optimum enema solution volume for the delivery of topically active drugs to the descending colon.

Microspheres of modified cellulose (DEAE), 40–160 μm in diameter, were laballed with [ 131 I]rose bengal and administered subcutaneously to rabbits. The release of the rose bengal was followed using gamma scintigraphy over a period of 28 days. Significant sustained tissue and blood levels were obtained.

In the present study the effect of food and specific gravity on the gastric retention time of floating (spec. grav. 0.96) and non-floating (spec. grav. 1.59) tablet formulations was investigated using gamma scintigraphy in humans. The results obtained indicate that the presence of food in the stomach appears to significantly prolong gastric retention of both the floating and non-floating tablets while specific gravity does not seem to play an important role in the residency time of the tablets in the stomach.

A solution of 99m Tc-labelled human serum albumin was administered into the nose as a spray and as one or three drops. The patterns of deposition and the rates of clearance in normal subjects were monitored by gamma scintigraphy. The spray was deposited mainly in the atrium, and cleared slowly into the pharynx. The single drop spread more extensively than the spray, while the three drops were sufficient to cover most of the walls of the nasal cavity. Clearance was faster following administration of the drops. These factors have implications when designing dosage regimens for drugs administered by the intranasal route.

The deposition of budesonide at fast (60 l min(-1)) and slow (301 min(-1)) inspiratory flow rates from Airmax, a new multi-dose dry powder inhaler, was compared with that from Turbuhaler and a standard pressurized metered dose inhaler (pMDI). Twelve patients with mild to moderate asthma took part in a five-way randomized crossover study, and inhaled a single nominal dose of 200 microg budesonide, labelled with 99mTc, on each study day. Deposition was determined by gamma scintigraphy. At the fast flow rate, Airmax and Turbuhaler deposited 25.8+/-6.5% (mean +/- sD) and 29.8+/-6.9%, respectively of the delivered dose in the whole lung (P = 0.080). At the slow flow rate, Airmax deposited 28.3+/-5.6%, Turbuhaler 22.7+/-5.6% and pMDI 12.1+/-3.4%. Using data on emitted doses determined in vitro, it was estimated that Airmax deposited 53.1+/-13.3 microg and 43.6+/-8-6 microg budesonide in the lungs at 60 l min(-1) and 30 l min(-1) respectively whilst Turbuhaler deposited 48.3+/-11.2 microg at 60 l min -and 24.2+/-6.0 microg at 30 l min(-1). In conclusion, lung deposition of budesonide from Airmax was comparable to that of Turbuhaler at a high flow rate but was markedly superior to Turbuhaler and pMDI at a lower flow rate. Unlike Turbuhaler, Airmax performs with relative flow-rate independence.

The efficacy of small portable nebulizers is often assumed by patients, pharmacists and physicians. Three healthy volunteers inhaled a mixture of sodium cromoglycate solution mixed with aqueous technetium-99 nebulized by each of three nebulizers and the distribution of radioactivity was detected by gamma scintigraphy. Unexpectedly large differences in the total amount of tracer delivered to the lungs were detected. The possible mechanisms and implications are discussed but it is clear that more information on the performance of individual nebulizers should be available.

Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents.

The release of a radiolabelled marker from an orally administered osmotic pump device (Osmet) has been evaluated in-vivo in a group of 6 subjects, using the technique of gamma scintigraphy. The duration of residence of the pump in the stomach was greatly influenced by food intake. However, the release of the marker from the device was independent of food and position within the gastrointestinal tract. Furthermore, the material released from the osmotic pump was well distributed in the gastrointestinal tract. Good agreement between in-vitro and in-vivo release rates was obtained.

The gastric emptying of a soluble and an insoluble component of a capsule formulation has been monitored by gamma scintigraphy using a dual isotope technique. There was no significant difference between the emptying rates for the two components or between fasting and non-fasting conditions (P > 001).

The transit of pellets of different densities (0.94 and l.96g cm-3) through the gastrointestinal tract of ileostomy subjects has been followed using the technique of gamma scintigraphy. In contrast with earlier reported results, the transit of the pellets was not affected by particle density.

Colonic transit of radiolabeled capsules has been monitored in 18 healthy subjects using gamma scintigraphy. The capsules ranged in volume from 0.3–1.8 cm3 and in density from 0.7–1.5 gcm−3. The capsules were administered after an overnight fast and entered the colon, on average, 5 h after dosing. Transit rates through the proximal colon were independent of capsule density. Any effect due to capsule volume was small when compared with intersubject variations in transit rates. Within 10 h of entering the colon 80% of the units had reached the splenic flexure. These findings have implications in the design of non-disintegrating, sustained release dosage forms.

Monoclonal antibody R11D10 to human cardiac myosin, which also cross-reacted with canine cardiac myosin, was used to demonstrate in vivo localization and visualization by gamma scintigraphy of experimental myocardial infarction. R11D10 Fab with a Ka of 5 X 10(8) M-1 was labeled with technetium-99m (99mTc) by the dithionite reduction method of technetium pertechnetate, via a bifunctional chelating agent, diethylene triamine pentaacetic acid (DTPA). Uptake of 99mTc R11D10 Fab in the infarct can be visualized as early as 2 h after intravenous administration. Comparison of R11D10 uptake to thallium-201, an analogue of potassium which is sequestered by normal myocardium, showed an inverse relation (r = -0.75, -0.87, -0.89), similar to that obtained with 125I labeled polyclonal antimyosin Fab. Ratios of R11D10 Fab in the infarct to normal myocardium were as high as 30:1 where access of antibody to antigen was not blood flow limited. However, with severe blood-flow restriction, the ratios were lower at about 10:1. Despite the theoretical limitation of a single epitope per myosin molecule available for binding by R11D10 Fab, the immense excess of myosin in the infarcted myocardium allowed adequate concentration of radiolabeled R11D10 for visualization of the infarct by external gamma scintiscanning.

The advanced delivery systems that are being developed for future clinical use are of increasing complexity and must be evaluated extensively by in vitro and in vivo tests. It is often necessary for research, development and regulatory purposes to have direct information in the following areas:- i. The position or distribution of the delivery system in the body ii. The integrity of the delivery system iii. The in vivo release characteristics

A method for monitoring the ocular distribution of solutions for ophthalmic use was developed using the technique of gamma scintigraphy. This method was used to monitor the effects of polyvinyl alcohol on the precorneal drainage of [99mTc]pertechnetate in the rabbit. The rate of drainage of solutions decreased on addition of PVA and precorneal residence of the marker was significantly prolonged, compared with saline controls, at a PVA concentration of 5% w/v. Increases in the activity in the inner canthal region mirrored the decrease in corneal counts. The method has a more general application for the study of ophthalmic formulations and devices in larger mammals and in man.

Free Na131 I and 131I-Albumin were injected in the cisterna magna of rhesus monkeys. The dynamics of descent into the spinal subarachnoid space and transport out of the cerebrospinal fluid were determined by gamma scintigraphy. 131I-Albumin moved slowly caudally, reaching the sacral CSF in three hours. Free Na131I was rapidly absorbed locally and did not descend. When its transport out of cerebrospinal fluid was inhibited by the addition of unlabeled isotonic Na I, 131I descended slowly at a rate parallel to that of tagged albumin. Injection of Na131I in hypertonic solutions caused immediate descent. Two minute periods of tumbling activity caused rapid movement of Na131I and 131I-Albumin into the lumbar spinal fluid. Na131I dynamics may serve as a model for other molecules actively transported out of cerebrospinal fluid, such as 5-hydroxy-indoleacetic acid; descent into caudal spinal fluid may depend on the degree of efflux from cerebrospinal fluid and on the animal's activity.

The gastric distribution and residence time of a new pectin-containing formulation, FF5005 (Farma Food A/S, Denmark), was investigated by using the technique of gamma scintigraphy in six healthy volunteers after administration with a radiolabelled meal. The formulation and test meal were radiolabelled with indium-113m and technetium-99m, respectively, and the formulation was administered to the subjects 30 min after the labelled meal. FF5005 was shown to float and form a discrete phase on top of the stomach contents and emptied from the stomach more slowly than the food (p less than 0.05, Wilcoxon signed rank test). The times taken for the formulation and test meal to half-empty from the stomach (T50) were 4.13 +/- 0.69 h (mean +/- SD) and 2.17 +/- 0.15 h (mean +/- SD), respectively. Greater than 50% of the formulation remained in the fundal region of the stomach for 3 h. FF5005 produced in vivo behaviour similar to that of established alginate-containing anti-reflux agents, and the pectin content of the formulation was shown to decrease the rate of emptying of the meal.

The gastrointestinal transit of a radiolabelled osmotic tablet drug delivery system has been monitored in groups of young and elderly healthy subjects, using gamma scintigraphy. The gastric emptying and small intestinal transit times were similar for both groups of subjects. The units were observed to move through the gastrointestinal tract at about the same rate as the released contents, arriving at the caecum on average 7 h after dosing. The data suggest that tablet adhesion to the mucosal surface is unlikely to be the mechanism responsible for the side effects reported for the indomethacin formulation Osmosin.

The influence of the putative bioadhesive, polycarbophil, on the gastric emptying of a pellet formulation, has been investigated in three fasted subjects. The pellets were radiolabelled with technetium-99m. Gastric emptying was measured using the technique of gamma scintigraphy. The pellets emptied from the stomach rapidly and in an exponential manner. Polycarbophil did not retard the gastric emptying of the pellets.

The appreciation of the behaviour of ophthalmic dosage forms in vivo has been limited by the lack of suitable quantitative methods. Tear sampling significantly alters the kinetics of the system because of the small volume of the tear film. The technique of gamma scintigraphy has superceded x-ray studies in the investigation of restriction of the nasolacrimal duct. It is a small step from this routine clinical application to apply the technique to the study of the precorneal behaviour of suitable markers incorporated into ophthalmic formulations. The method is associated with a low radiation dosimetry and can be safely used in man. This affords the opportunity to conduct comparative studies of the behaviour of polymeric formulations in man with established animal models such as the rabbit.

In routine postoperative observations on 31 transplanted kidneys, computed tomography (CT), ultrasonography (US) and gamma scintigraphy (GS) were compared with respect to diagnosis of abscess or lymphocele in the vicinity of the transplant, rejection and outflow obstruction. The results showed that US was the most reliable procedure for detecting fluid-filled cavities. In cases of graft rejection, GS was of most value. In demonstrating outflow obstruction, there was no definite difference between the three methods.

By using 99mTc in gamma scintigraphy it is possible to visualize different processes in the brain. However, malignant and benign cerebral lesions cannot be differentiated by means of 99mTc scintigrams. Some authors C(avalieri, Perez-Modrego, Frederiksen) have used sodiumselenite (Se-75) in the scanning of tumours situated in different parts of the body. They were able to visualize about 2/3 of malignant tumours by using this isotope.

Nasal solutions of almotriptan malate were prepared in phosphate buffer containing different proportions of HPMC E15. In vitro permeation studies were performed using Franz diffusion cell with dialysis membrane and ex vivo permeation studies were carried out using sheep nasal mucosal layer. The formulations were radiolabeled with 99mTc and the nasal residence time was studied in rabbits. Nasal irritation was evaluated in rats. Formulations prepared with HPMC E15 5% w/v did not retard the release of almotriptan. Gamma scintigraphy studies showed increased residence time as compared to plain drug solution. No nasal irritation was observed and the formulations were found stable for 3 months.

The recently reported amphiphilic chelate, $[Gd(EPTPAC_{16})(H_2O)]^{2-}$, forms supramolecular aggregates in aqueous solution by self-assembly of the monomers with a relaxometrically determined critical micellar concentration (CMC) of 0.34 mM. The effect of sonication on the aggregate size was characterized by dynamic light scattering and relaxometry, indicating the presence of premicellar aggregates and an overall decrease in aggregate size and polydispersity upon sonication, slightly below the CMC. $\{[^{153}Sm](EPTPAC_{16})(H_2O)\}^{2-}$ radiotracer was evaluated in vivo from $\gamma$ scintigraphy and biodistribution in Wistar rats. It was found to depend strongly on the sample concentration, below or above the CMC, and its sonication, in a way that correlates with the effect of the same factors on the size of the aggregates formed in solution. Below CMC, the very large aggregates of the $[^{153}Sm]^{3+}$-labeled chelate were persistently and mainly taken up by the lungs, and also by the macrophage-rich liver and spleen. Sonication of this solution led to loss of the lung uptake. Above CMC, the metal chelate was mainly taken up by the liver, with very little uptake by the spleen and lungs. In vivo, dynamic contrast-enhanced (DCE)-MRI evaluation of the micellar $[Gd(EPTPAC_{16})(H_2O)]^{2-}$ compound in Wistar rats showed a persistent hepatic positive-contrast effect in $T_1$-weighted images, qualitatively similar to the clinically established $Gd^{III}$-based hepatobiliary-selective agents. No enhancement effect was observed in the lungs because of the scarcity of mobile protons in this organ, despite the scintigraphic evidence of significant lung retention of the $[^{153}Sm]^{3+}$-labeled chelate at concentrations below the CMC. © 2007 John Wiley & Sons, Ltd

Oesophageal transit has been studied in six asymptomatic subjects aged 29–80 years. Using gamma scintigraphy, the transit of a liquid and five small tablets was monitored in each subject. All the subjects exhibited normal liquid swallowing, with 50% oesophageal clearance times of less than 5 s. In three subjects all the tablets passed through the oesophagus within 6 s, but transit was prolonged in 60% of the swallows in the other subjects. Tablet hold up occurred more frequently in the elderly. An additional drink of water cleared all lodged tablets into the stomach. To minimize possible mucosal irritation, the taking of even small tablets should be followed by an additional drink of water.

The sensitivity of standard radiography for the study of oleic acid (OA) induced canine acute respiratory distress syndrome (ARDS) and the effect of positive and expiratory pressure (PEEP) on the radiographic appearance was investigated. Comparison was made with similar study done with computerized gamma camera following intravenous injection of 99mTC-human serum albumin (HSA) in canine oleic acid induced pulmonary capillary protein leak and pulmonary edema. Three dogs were studied at each of the following doses of OA: 0.06, 0.10, and 0.20 ml/kg. Ten cm PEEP was applied for 1/2 hour, 1/2 hours after OA. A-P chest radiographs were obtained at 1/2 hour intervals and 5 min. after PEEP was applied and discontinued. Standard radiography was able to detect OA induced ARDS within 1/2 hour in each animal given 0.2 ml/kg OA. In only 1 of 3 dogs given 0.05 ml/kg could any changes be detected over the 90 min. of study. Immediately following the application of PEEP, a marked reduction in the apparent severity of ARDS was seen in each animal which was reversed shortly after PEEP was released. Blood gasses did not deteriorate until a dose of 1.10 ml/kg was reached. Gamma scintigraphy was able to detect a marked protein leakage at 0.05 ml/kg OA. In conclusion, standard radiography can detect ARDS but is less sensitive than gamma scintigraphy and can be markedly altered with PEEP.