Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in a pig model.

BACKGROUND: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13N-ammonia (13NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS: Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(-1). The extent of defects induced by left anterior descending coronary artery constriction measured by 18F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS: 18F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of 18F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics.

AIM: Radiation exposure to the kidney limits therapy with radiometal labelled DOTATOC. This study evaluates the organic anion and cation transport (inhibitors: probenecid and cimetidine/dexamethasone) as well as diuresis (furosemide and mannitol) regarding renal uptake of [(111)In]DOTATOC. METHODS: One hundred eight male Fisher rats were injected with [(111)In]DOTATOC via the tail vein. Prior to activity injection a total of 84 rats underwent injection with probenecid vs. sodium chloride 0.9% (48 rats), cimetidine vs. dexamethasone vs. sodium chloride 0.9% (18 rats), and furosemide vs. mannitol vs. sodium chloride 0.9% (18 rats). Rats were sacrificed at predetermined time points up to 48 h after activity injection. Kidneys, adrenal glands, pancreas, spleen, blood, liver, and muscle were harvested and injected activity per gram tissue was determined. Autoradiographic images of the kidneys were acquired in a total of 24 rats. RESULTS: Probenecid led to a reduction in renal uptake by up to 30% while not significantly changing the activity accumulation in the other organs investigated. This reduction was attributable to the renal cortex (ratio cortex/medulla 1.72 vs. 1.99; p = 0.006). Cimetidine and dexamethasone had no effect in any of the organs. Furosemide led to a 44% increase in renal activity accumulation attributable to enhanced renal medullary uptake (ratio cortex/medulla 1.44 versus 1.69; p = 0.006). Mannitol had no effect on renal activity uptake. CONCLUSION: Inhibition of the organic anion transport by probenecid may help reduce renal uptake regarding therapy with radiometal labelled DOTATOC. The enhancing effect of furosemide may be unfavourable for therapy. The results must be confirmed by human studies.

Proof of principle for the use of 11C-labelled peptides in tumour diagnosis with PET.

PURPOSE: The future significance of peptide radiopharmaceuticals in diagnostic imaging with PET will be dependent on methodological aspects, as well as other requirements such as availability of the radionuclide and cost-effectiveness of its production. The aim of this study was to evaluate whether recent improvements in the modification of peptide pharmacokinetics by carbohydration may open a niche for the use of 11C-labelled peptide receptor binding tracers. METHODS: A carbohydrated analogue of Tyr3-octreotate was used as a clinically relevant peptide. Oxime-mediated coupling between 4-[11C]methoxy-benzaldehyde and an aminooxy-conjugated peptide precursor provided the 11C-labelled peptide in 21+/-5% decay-corrected yield (n=4) in a synthesis time of about 1 h. RESULTS: In rat pancreas carcinoma xenografted mice, the compound displayed predominant and fast renal clearance combined with high tumour uptake (18.5+/-2.8% ID/g) at 30 min post injection. Corresponding values for kidney, liver and intestine were 18.5+/-2.4% ID/g, 3.2+/-0.5% ID/g and 2.1+/-0.3% ID/g, respectively. In a PET study with xenografted mice, the tumour (0.2-0.3 g) was clearly delineated as early as 20 min after injection. Somatostatin receptor (sstr)-specific uptake was demonstrated by reduction of tumour uptake to 20% of control by co-injection of TOC (0.4 mg/kg; 30 min p.i.). CONCLUSION: A 11C-labelled octreotate derivative has been prepared which shows suitable pharmacokinetics for in vivo imaging of sstr-overexpressing tumours and thus represents the first proof of principle for the potential of 11C-labelled peptides in tumour imaging.