Objective comparison of lesion detectability in low and medium-energy collimator iodine-123 mIBG images using a channelized Hotelling observer.

Iodine-123 mIBG imaging is widely regarded as a gold standard for diagnostic studies of neuroblastoma and adult neuroendocrine cancer although the optimal collimator for tumour imaging remains undetermined. Low-energy (LE) high-resolution (HR) collimators provide superior spatial resolution. However due to septal penetration of high-energy photons these provide poorer contrast than medium-energy (ME) general-purpose (GP) collimators. LEGP collimators improve count sensitivity. The aim of this study was to objectively compare the lesion detection efficiency of each collimator to determine the optimal collimator for diagnostic imaging. The septal penetration and sensitivity of each collimator was assessed. Planar images of the patient abdomen were simulated with static scans of a Liqui-Phil™ anthropomorphic phantom with lesion-shaped inserts, acquired with LE and ME collimators on 3 different manufacturers' gamma camera systems (Skylight (Philips), Intevo (Siemens) and Discovery (GE)). Two-hundred normal and 200 single-lesion abnormal images were created for each collimator. A channelized Hotelling observer (CHO) was developed and validated to score the images for the likelihood of an abnormality. The areas under receiver-operator characteristic (ROC) curves, Az, created from the scores were used to quantify lesion detectability. The CHO ROC curves for the LEHR collimators were inferior to the GP curves for all cameras. The LEHR collimators resulted in statistically significantly smaller Azs (p < 0.05), of on average 0.891 ± 0.004, than for the MEGP collimators, 0.933 ± 0.004. In conclusion, the reduced background provided by MEGP collimators improved 123I mIBG image lesion detectability over LEHR collimators that provided better spatial resolution.

Simultaneous dual-radionuclide myocardial perfusion imaging with a solid-state dedicated cardiac camera.

PURPOSE: We compared simultaneous dual-radionuclide (DR) stress and rest myocardial perfusion imaging (MPI) with a novel solid-state cardiac camera and a conventional SPECT camera with separate stress and rest acquisitions. METHODS: Of 27 consecutive patients recruited, 24 (64.5+/-11.8 years of age, 16 men) were injected with 74 MBq of (201)Tl (rest) and 250 MBq (99m)Tc-MIBI (stress). Conventional MPI acquisition times for stress and rest are 21 min and 16 min, respectively. Rest (201)Tl for 6 min and simultaneous DR 15-min list mode gated scans were performed on a D-SPECT cardiac scanner. In 11 patients DR D-SPECT was performed first and in 13 patients conventional stress (99m)Tc-MIBI SPECT imaging was performed followed by DR D-SPECT. The DR D-SPECT data were processed using a spill-over and scatter correction method. DR D-SPECT images were compared with rest (201)Tl D-SPECT and with conventional SPECT images by visual analysis employing the 17-segment model and a five-point scale (0 normal, 4 absent) to calculate the summed stress and rest scores. Image quality was assessed on a four-point scale (1 poor, 4 very good) and gut activity was assessed on a four-point scale (0 none, 3 high). RESULTS: Conventional MPI studies were abnormal at stress in 17 patients and at rest in 9 patients. In the 17 abnormal stress studies DR D-SPECT MPI showed 113 abnormal segments and conventional MPI showed 93 abnormal segments. In the nine abnormal rest studies DR D-SPECT showed 45 abnormal segments and conventional MPI showed 48 abnormal segments. The summed stress and rest scores on conventional SPECT and DR D-SPECT were highly correlated (r=0.9790 and 0.9694, respectively). The summed scores of rest (201)Tl D-SPECT and DR-DSPECT were also highly correlated (r=0.9968, p<0.0001 for all). In six patients stress perfusion defects were significantly larger on stress DR D-SPECT images, and five of these patients were imaged earlier by D-SPECT than by conventional SPECT. CONCLUSION: Fast and high-quality simultaneous DR MPI is feasible with D-SPECT in a single imaging session with comparable diagnostic performance and image quality to conventional SPECT and to a separate rest (201)Tl D-SPECT acquisition.

Cardiac 82Rubidium PET/CT: initial European experience.

PURPOSE: Myocardial perfusion with PET/CT has advantages over conventional SPECT. We describe our initial European experience using (82)Rubidium-PET/CT, as part of a clinical myocardial perfusion service. METHODS: We studied the first 100 patients (64 male; 36 female, mean age = 60: SD +/-12.5y, mean body mass index = 30: SD +/-6.9kg/m( 2 )) who underwent (82)Rubidium cardiac PET/CT in our institution. Thirty patients had recently undergone coronary angiography. Patients underwent imaging during adenosine infusion and at rest. Images were acquired over 5 minutes using a GE-PET/CT instrument. Image quality was described as good, adequate or inadequate. Images were reported patient-by-patient by a minimum of five nuclear medicine physicians. A segment-by-segment analysis (17-segment model) was also performed. RESULTS: Image quality was good in 77%, adequate 23% and inadequate 0%. There was no statistical difference in image quality between obese and non-obese patients (Fisher's exact test, p = 0.2864). 59% had normal perfusion studies, 29% had inducible ischaemia, 12% had myocardial infarction (11% with super added ischaemia). There was reduced (82)Rubidium uptake in 132/1700 segments during stress. There was reduced (82)Rubidium uptake at rest in 42/1700 segments. The (82)Rubidium PET/CT findings were consistent with the angiographic findings in 28/30 cases. CONCLUSION: We show that, even from initial use of (82)Rubidium, it is possible to perform myocardial perfusion studies quickly with good image quality, even in the obese. The PET findings correlated well in the third of the cases where angiography was available. As such, (82)Rubidium cardiac PET/CT is likely to be an exciting addition to the European nuclear physician/ cardiologist's radionuclide imaging arsenal.

The use of formulation technology to assess regional gastrointestinal drug absorption in humans.

The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract.

Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal transit and drug absorption.

PURPOSE: The aim of the study was to investigate the effect of different concentrations of polyethylene glycol 400 (PEG 400) on liquid transit through, and ranitidine absorption from, the gastrointestinal tract. METHODS: Six healthy male volunteers received, on four separate occasions, 150 mL water containing 150 mg ranitidine and either 0 (control), 1,2.5, or 5 g PEG 400. The solutions were radiolabeled with technetium-99m to allow their gastrointestinal transit to be followed using a gamma camera. Urine samples were collected over a 24-h period to assess the amount of ranitidine excreted and hence absorbed. RESULTS: No significant differences in gastric emptying were noted between the four solutions. In contrast, the presence of 1, 2.5, and 5 g PEG 400 reduced the mean small intestinal transit times of the solutions by 9, 20, and 23%, respectively, against the control. In terms of drug absorption, the mean cumulative amount of ranitidine excreted was reduced by 38% in the presence of both 2.5 and 5 g PEG 400, although it was significantly increased by 41% in the presence of 1 g PEG 400. CONCLUSIONS: The results show that low concentrations of PEG 400 enhance the absorption of ranitidine possibly via modulation of intestinal permeability, while high concentrations have a detrimental effect on ranitidine absorption presumably via a reduction in the small intestinal transit time.

Influence of polyethylene glycol 400 on the gastrointestinal absorption of ranitidine.

PURPOSE: To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical excipient previously shown to accelerate small intestinal transit, on the absorption characteristics of ranitidine from the gastrointestinal tract. METHODS: Ten healthy male volunteers each received, on two separate occasions, an immediate-release pellet formulation of ranitidine (150 mg) encapsulated within a hard gelatin capsule and a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). The liquid preparations were also radiolabelled with indium-III to allow their transit through the gastrointestinal tract to be followed using a gamma camera. On a further occasion an intravenous injection of ranitidine (50 mg) was administered. Blood samples were taken over a 12 h period on each study day to allow a ranitidine plasma and subsequent absorption rate profile to be generated for each oral formulation. Urine was collected for 24 h and assessed for PEG 400 concentration. RESULTS: The absolute bioavailability of ranitidine from the pellet formulation was significantly reduced by 31% (from 51% to 35%) and small intestinal liquid transit time was significantly shortened by 37% (from 226 min to 143 min) as a consequence of PEG 400 in the test preparation. PEG 400 also affected the rate of ranitidine absorption, with major differences noted in the mean absorption time and Cmax parameters. The appearance of double peaks were less evident in the ranitidine pharmacokinetic profiles in the presence of PEG 400, and little or no correlation was observed between the absorption of ranitidine and PEG 400. CONCLUSIONS: These results clearly demonstrate that PEG 400 adversely influences the gastrointestinal absorption of ranitidine. This in turn has ramifications for the use of PEG 400 as a pharmaceutical excipient in oral formulations.