Technetium-99m-tetrofosmin: retention of nitrogen atmosphere in kit vial as a cause of poor quality material.

Technetium-99m (99Tc(m))-tetrofosmin was prepared using four different reconstitution methods. The radiochemical purity (RCP) of these products was assessed 8 h later using thin layer chromatography (TLC). Material produced using the original method supplied by the manufacturer and using an newer method, which involves the use of a vent needle and the addition of air, had acceptable RCP (mean +/- SD 94.2 +/- 1.1% and 94.7 +/- 1.7%, respectively) and similar chromatograms. In addition, both products showed good clinical efficacy and exhibited normal biodistribution behaviour. Preparing 99Tc(m)-tetrofosmin using the two other methods, one using a high radioactive concentration and the other maintaining the nitrogen content of the kit vial, gave rise to chromatograms with reduced RCP (63.5 +/- 10.9% and 61.9 +/- 7.6%, respectively) and greater levels of impurities. Although neither of these last two preparations was used clinically, we suggest that reports of poor quality images may be the result of administration of materials similar to these. Results for the high radioactive concentration method were as expected and are consistent with the restrictions imposed by the manufacturer. However, results using the last method are surprising and would suggest that the production of good quality 99Tc(m)-tetrofosmin is dependent on the quantity of nitrogen in the kit vial. We believe that the amount of nitrogen removed from the kit vial during the process of reconstitution is critical. If too much nitrogen is present this will result in poor quality material. In practice it is conceivable that there could be occasions when insufficient nitrogen is removed when following the manufacturer's original guidance, thereby leading to low RCP material. To ensure adequate nitrogen is removed during reconstitution, adoption of the manufacturer's revised method, involving the deliberate introduction of air, is therefore appropriate.

No-carrier-added 123I-MIBG: an initial clinical study in patients with phaeochromocytoma.

Radioiodinated meta-iodobenzylguanidine (MIBG) is used routinely for imaging and targeted radiotherapy of tumours derived from the neural crest. Since active uptake of MIBG by the noradrenaline transporter (NAT) makes a greater contribution to total drug accumulation than passive uptake when MIBG is present at low concentrations, tumour-specific uptake should be enhanced by the administration of lower molar amounts of MIBG. This could be achieved through the use of MIBG with a high specific activity. Commercially available preparations of 123I-MIBG have specific activities of approximately 200 MBq.mg-1. We have synthesized and used no-carrier-added (n.c.a.) 123I-MIBG produced by an iododesilylation reaction (specific activity 0.7 TBq.mg-1). We report here the first clinical studies comparing the commercially available and n.c.a. MIBG diagnostic preparations. Five patients with known phaeochromocytoma were studied. Unlike studies in animal models, no consistent improvement in tumour uptake was observed with the n.c.a. material. A larger patient group is required to determine whether there are significant differences between the two preparations, before proceeding to studies at therapeutic activity levels of n.c.a. 131I-MIBG. Even with no improvement in tumour uptake, n.c.a. MIBG may be the favoured formulation for therapeutic applications to reduce the molar amount of drug injected.

Prognostic value of single-photon emission tomography in acute ischaemic stroke.

Single-photon emission tomography (SPET) is widely used in the investigation of acute stroke. We investigated the relationship between SPET data and functional outcome in a large group of acute stroke patients. One hundred and eight patients underwent cerebral computed tomography (CT) and technetium-99m hexamethylpropylene amine oxime SPET after acute ischaemic stroke. We categorised the clinical presentation according to the Oxford classification of acute stroke. Outcome was measured 1 year after stroke using mortality and the Barthel Index for survivors. SPET scans were interpreted without reference to the clinical data using a semi-automatic technique. Three experienced observers determined the presence of luxury perfusion using suitably scaled SPET images in conjunction with the CT scan. Both SPET volume and severity of deficit were significantly negatively correlated with Barthel Index at 1 year (rs=-0.310, P<0.0001, and rs=-0.316, P<0.0001 respectively). In patients scanned with SPET within 16 h of stroke onset, the correlations were more strongly negative (rs=-0.606, P<0. 001, and rs=-0.492, P<0.005 respectively). Luxury perfusion was not associated (chi2=0.073, df=1, P=0.79) with good functional outcome (Barthel score >/=60). Stepwise logistic regression identified Oxford classification, total deficit volume and patient's age as significant predictors of functional outcome. Overall predictive accuracy was 72%. Predictive accuracy was better in patients who received SPET within 16 h of stroke onset. SPET provides useful information about the functional outcome of acute stroke at 1 year. However, the accuracy of prediction decreases the longer SPET is delayed. Prognostication using SPET in combination with clinical assessment and other investigations may also be considered.

The radiation dose to the urinary bladder in radio-iodine therapy.

A new MIRD dynamic model has been used to provide estimates of the dose to the urinary bladder resulting from the administration of the therapeutic agents 131I as iodide (for thyroid carcinoma) and 131I meta-iodobenzylguanidine (MIBG) (for neuroendocrine tumours). Because the latter agent is used for therapeutic purposes in children, dose estimates were obtained for subjects aged 1 year and upwards. Those parameters likely to influence the bladder dose were also investigated, making use of the inherent flexibility of the model. For an administration of 1 GBq of either 131I as iodide or 131I MIBG to an adult subject, the radiation dose to the inner surface of the bladder was estimated to be approximately 1100 mGy, which is nearly twice the value estimated using a constant-volume bladder model. The new model produced dose estimates for children (within the range 1000-2750 mGy GBq-1 of 131I MIBG) which were approximately 50% greater than those derived using a constant-volume bladder model. The urine flow rate was found to have the greatest effect on the bladder dose, a flow of twice the normal rate resulting in a reduction in the bladder dose by a factor of two. On the other hand, a reduction in the urine flow rate to half the normal value was estimated to increase the radiation dose by a factor of two. This was true for subjects of all ages. With normal voiding, the average dose to the bladder wall from 131I beta-radiation was estimated to be 5-13% of the surface beta dose for subjects of different ages, the values being greater in children. This has to be compared with a photon contribution to the average bladder wall dose amounting to 10-20% of the combined surface dose both from beta-particles and from photons.

Dosimetric considerations in 131I-MIBG therapy for neuroblastoma in children.

Dosimetric calculations have been made for organ doses in patients receiving 131I-MIBG therapy as treatment for neuroblastoma. As well as whole body and liver dose, consideration has been given to dosimetry of organs (lung, urinary bladder) whose tolerance may become treatment limiting when 131I-MIBG is given as part of combined modality therapy. Data from both adults and children receiving radiolabelled MIBG for diagnostic or therapeutic purposes have been compared in constructing dosimetry models for children. A recently published urodynamic model has been used in the estimation of radiation dose to the bladder. The results show that liver and lung may receive doses greater than the average total body dose (0.58 mGy MBq-1 and 0.35 mGy MBq-1, respectively, as compared with 0.25 mGy MBq-1 to the whole body). The organ dose estimates do not differ greatly from previous analyses except in the case of the bladder for which the new modelling studies have resulted in lower dose estimates (0.76 mGy MBq-1 administered, for dose to bladder surface from bladder contents) than in some published series. This may result from differing assumptions regarding parameters such as bladder content and urine flow rate, an enhanced fluid intake being assumed in the present bladder dose estimates. Average doses to the bladder wall from the contents were estimated to be 7.4-11.3% of the surface doses. The urodynamic modelling analysis shows that the bladder could receive a much greater dose (by an order of magnitude) in patients who were inadequately hydrated or had impaired renal function.