This report is the conclusion of the international consensus committee on renal transit time (subcommittee of the International Scientific Committee of Radionuclides in Nephrourology) and provides recommendations on measurement, normal values, and analysis of clinical utility. Transit time is the time that a tracer remains within the kidney or within a part of the kidney (eg, parenchymal transit time). It can be obtained from a dynamic renogram and a vascular input acquired in standardized conditions by a deconvolution process. Alternatively to transit time measurement, simpler indices were proposed, such as time of maximum, normalized residual activity or renal output efficiency. Transit time has been mainly used in urinary obstruction, renal artery stenosis, or renovascular hypertension and renal transplant. Despite a large amount of published data on obstruction, only the value of normal transit is established. The value of delayed transit remains controversial, probably due to lack of a gold standard for obstruction. Transit time measurements are useful to diagnose renovascular hypertension, as are some of the simpler indices. The committee recommends further collaborative trials.

Purpose Radiolabelled interleukin-2 is a radiopharmaceutical used for the study of chronic inflammatory processes. 123 I-labelled interleukin-2 has successfully been used in a large number of patients affected by several immune-mediated diseases. 123 I, however, is expensive and not readily available. We have, therefore, developed a method for labelling interleukin-2 with 99m Tc to high specific activity based on the use of an N 3 S bifunctional chelating agent. In this paper, we describe the results obtained with 99m Tc-interleukin-2 in a series of eight normal subjects and of 12 patients with autoimmune thyroid diseases. Methods Biodistribution, pharmacokinetics, haematological and systemic toxicity, radiation absorbed dose and in vivo targeting were studied. Results Results showed rapid plasma clearance of 99m Tc-interleukin-2 with retention mainly in the kidneys. Biodistribution and kinetics were similar to that observed for 123 I-interleukin-2. No acute systemic toxicity was found; a small decrease in peripheral blood lymphocytes was observed in the first hours only in patients, but it was mild and transient. 99m Tc-interleukin-2 accumulated, to varying extents, in the thyroid of all patients affected by autoimmune thyroid diseases but not in the thyroid of normal subjects. The effective dose equivalent of a diagnostic activity of 99m Tc-interleukin-2 (185 MBq) was 1.35 mSv. No correlation was observed between thyroid autoantibodies and uptake of 99m Tc-interleukin-2. Conclusions The use of 99m Tc-interleukin-2 is safe and simple; the favourable dosimetry and biodistribution and the rapid clearance make it potentially useful for the study of chronic inflammatory diseases such as autoimmune thyroid disease.

Aim: To analyse the clinical outcome and myocardial perfusion and function after transmyocardial revascularisation (TMR) in patients with normal left ventricular function and multivessel coronary artery disease non-amenable for standard revascularisation. Method and results: Twenty three severely symptomatic patients (CCS score median 4) with normal left ventricular systolic function but coronaries non-amenable for either PTCA or CABG were subjected to TMR. The angina score, left ventricular systolic and diastolic function in radionuclide ventriculography at rest, exercise tolerance and myocardial perfusion - Thallium-201 SPECT (adenosine stress 74 and 37 MBq under nitrate cover) were evaluated before and 3, 6, 12 months post-operatively. After an average of 40 +/- 12 (range 14-56) TMR channels angina score decreased significantly (p < 0.0001) and the exercise tolerance increased (from 6.0 +/- 4.5 to 9.1 +/- 4.6 after 6 months, p < 0.05) in 21 patients. During the follow up period two patients had a myocardial infarction and one committed suicide after 6 months. Ejection fraction dropped significantly only after 1 year post-TMR from 70 +/- 13 to 63 +/- 0.13%, p < 0.05. The overall perfusion improved initially in 14 patients with subsequent deterioration in time. The changes in segmental perfusion were not associated with the symptomatic improvement. Conclusion: Transmyocardial revascularisation in patients with normal ejection fraction may improve the angina class, exercise tolerance and overall but not segmental perfusion and does not show any immediate effect on left ventricular function.

UNLABELLED One of the potential limitations in the usefulness of both renal output efficiency (ROE) and normalized residual activity (NORA) is their residual dependence on total renal function. The purpose of this study was to present and examine a new quantitative method whereby the effects of this dependence may be removed. METHODS The analytic method involves the determination of a retention function using an unconstrained matrix algorithm deconvolution technique followed by reconvolution with a chosen standard input function to yield a new secondary renal activity time (A/T) curve from which normalized values of ROE and NORA, denoted as N_ROE and N_NORA, respectively, can then be obtained using conventional definitions. The method has been applied in a series of 50 patient studies, which had been acquired using (99m)Tc-mercaptoacetyltriglycine (99(m)Tc-MAG3) and a standard F+18 furosemide protocol, with values of the ratio of plasma clearance to plasma volume (C/V) in the range 0.013-0.242 min(-1). RESULTS Pre- and postnormalization values of NORA, calculated at 30 min after injection, showed a significant difference in mean values (paired t test; P < 0.001), with a maximum observed difference, DeltaNORA(30), of -4.82 (-482%) and with a SD on the paired differences, DeltaNORA(30), of 0.56 (56%) or 0.63 (63%) if background subtraction on the input function (BSIF) had been performed. In contrast, corresponding values of ROE showed a nonsignificant difference in means (P > 0.05) and a SD on the paired differences, DeltaROE(30), of 3.7% or 3.2% with and without BSIF, respectively. The normalized parameters N_ROE and N_NORA were found to be strongly linearly correlated (r = -0.99; P < 0.001), in agreement with theoretical predictions. CONCLUSION These results suggest that renal function affects NORA significantly more than ROE. The effects can be corrected by our normalization technique, resulting in equivalent values of normalized ROE and normalized NORA.

The goal of this work was to determine an optimal radioimmu- notherapy agent for further development against non-Hodgkin's lymphoma. We sought to establish the stability profile of 90Y- labeled humanized LL2 (hLL2) monoclonal antibody (mAb) when prepared with different chelating agents and, from these data, to estimate the dosimetric improvement to be expected from use of the most stable 90Y-chelate-hLL2 complex. Methods: The complementarity-determining region- grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to 3 dif- ferent chelating agents, 2 of which were derivatives of diethyl- enetriaminepentaacetic acid (DTPA) and 1 of which was the macrocyclic chelate 1,4,7,10-tetraazacyclododecane-N,N,N,N- tetraacetic acid (DOTA). The 3 hLL2 conjugates were radiola- beled with 90Y and tested for stability in vitro against a 10,000- fold molar excess of free DTPA over 9 d. They were also tested against normal human serum at 37°C over 12 d. Each conjugate was radiolabeled with the -emitting radionuclide, 88Y, and compared for biodistribution in normal and lymphoma xeno- graft- bearing athymic mice. In vivo data were analyzed for statistical differences in the uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each complex. Results: 90Y-DOTA complex of the hLL2 mAb was completely stable to either DTPA or serum challenge for the duration of either experiment (equivalent to 3.3- 4.5 half-lives of 90Y radionuclide or 90% of possible 90Y decays from any initial starting activity). Complexes of hLL2 that had been prepared using the DTPA-type chelates lost 3%- 4% of initially bound 90Y over the first few days and about 10%-15% over the duration of the challenges. In vivo, these stability differences manifested as significantly lower yttrium uptake in bone and cortical bone over a 10-d period when DOTA was used as the yttrium chelating agent. Absorbed doses per 37 MBq (1 mCi) of 90Y-mAb were 3,555 and 5,405 cGy for bone and 2,664 and 4,524 cGy for washed bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, re- spectively, amounting to 52.0% and 69.8% increases in ab- sorbed radiation doses for bone and washed bone, respec- tively, when a DOTA chelate was switched to a Mx-DTPA chelate. Conclusion: 90Y-hLL2 prepared with the DOTA chelate represents an improved agent for radioimmunotherapy of non- Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, compared with 90Y- hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this benefit will result in a substantial toxicologic advantage for a DOTA-based hLL2 con- jugate.

Aim: To test prospectively 123I imaging follow-up of DTC. Method: One hundred and seven studies were evaluable in 82 patients (female/male ratio 3.5:1, papillary/follicular/mixed/hurtle cell tumour ratio 13:5:2:1) using 185 MBq 123I imaging at 2 and 24 h. Results: Seventy-four studies were 123I negative (51 6 months post-ablation, 23 post-previous 131I therapy). Four showed high thyroglobulin with radiology/MIBI evidence of disease but no further 131I treatment given. Seven studies were positive (4 completed 131I therapy, 3 awaiting therapy). Twenty-six patients had both 123I imaging and 131I therapy. Twenty-two were 123I positive and post-131I therapy scan positive (greater uptake with 131I than 123I in 4). Three studies were 123I negative, post-131I therapy scan negative. One patient 123I negative with low TSH had post-131I therapy scan positive three months later. Combining these 26 studies with our previous 17 similar studies including 131I tracer negative scans gave 36 concordant 123I pre/131I post-therapy positive scans, 5 concordant negative scans and 2 discordant results, 43 studies, χ2=28, P<0.001. Conclusion: High dose 123I imaging is an excellent predictor of the post-131I therapy scan and when strategically combined with thyroglobulin has replaced 131I tracer studies in our follow-up of DTC.

s of the 31st Annual Meeting of the British Nuclear Medicine Society, Manchester, UK, 29 April to 1 May 2003 - POSTER PRESENTATIONS

The aim of the study was to assess the effect of transmyocardial laser revascularization (TMLR) alone and in combination with coronary artery bypass grafting (CABG) on the angina score (CCS--Canadian Cardiovascular Society class), exercise tolerance and left ventricular function 6 months after the procedures. Sixty two patients were subjected to revascularization, 38 to sole TMLR procedure and 24 to combination CABG and TMLR (CABG/TMLR group). The angina score and exercise stress test together with radionuclide ventriculography were performed before and 6 months after the operation. The angina class and exercise tolerance were similar in both groups preoperatively. After the operation the improvement was seen in both groups with no statistical difference. The left ventricular ejection fraction were 61 +/- 8% and 54 +/- 8% (p < 0.05) before operation and after 6 months respectively. Transmyocardial laser revascularisation alone and in combination with coronary artery bypass grafting may relieve the angina and improve the exercise tolerance. However the left ventricular ejection fraction may drop significantly.

BACKGROUND Gated single photon emission tomography (SPET) may simultaneously assess perfusion and function of the myocardium. AIM To evaluate the relationship between the presence of ischaemia during an adenosine stress test and the changes in left ventricular (LV) function obtained after stress and at rest with gated SPET by using adenosine same-day stress and rest protocol. METHODS The study population consisted of twenty eight patients. The gated SPET acquisition was performed both after adenosine vasodilatation and at rest with a protocol as follows: 300 MBq of Tc-99m Myoview at stress, 700 MBq reinjection at rest and double head gamma camera. Global left ventricular ejection fraction (LVEF) and end-diastolic and end-systolic volumes (EDV, ESV) as well as the regional wall motion reversibility from post-stress and resting scan were analysed. RESULTS Wall motion disturbances were present in the stress study in 15 patients with subsequent improvement in 14 cases on the rest scans. An independent evaluation of the perfusion data revealed significant reversible myocardial ischaemia in 18 patients and negative result in 10. There was a significant difference between EDV change in patients with or without ischaemia (p<0.02). The post-stress LVEF and ESV were significantly different from those measured at rest. Reversible regional wall motion impairment indicated the presence of significant reversible myocardial ischaemia with an 88% positive predictive value (70% and 75% for sensitivity and specificity, respectively). CONCLUSIONS The post-stress LVEF with gated SPET may not reflect true resting measurements. The qualitative assessment of regional wall motion reversibility shows better correlation with the ischaemic scan pattern than the difference in the LVEF and may be helpful in assessing the significance of reversible myocardial ischaemia.

BACKGROUND:The effect of adenosine and exercise on gated SPET left ventricular ejection fraction (LVEF), end diastolic volume (EDV) and end systolic volume (ESV) has not been fully investigated. The aim of the study was to compare functional measurements obtained in one-day adenosine rest and two-day stress-rest protocols in relation to ischaemia.MATERIAL AND METHODS:Out of 226 consecutive patients examined with submaximal treadmill stress-rest 700 MBq Tc-99m MIBI, 26 were chosen to match those subjected to adenosine (140 micro g/kg/min) enhanced by a low level exercise protocol (300 MBq and 700 MBq Tc-99m tetrofosmin for stress and rest respectively). All images were acquired on a double head system and were gated using 8 frames, 25 s per frame.RESULTS:ED and ES volumes increased after adenosine but decreased after treadmill resulting in the post-stress LVEF being significantly greater than after adenosine, 60 +/- 11 v. 51 +/- 13% (p < 0.01). This was caused by the smaller post-stress ESV in the treadmill group 40 +/- 20 v. 51 +/- 34, p < 0.05. In non-ischaemic scans the LVEF was greater (61 +/- 8 v. 51 +/- 14, p < 0.01) and EDV and ESV smaller after both stress and rest.CONCLUSIONS:The adenosine test may have an opposite influence on the EDV and ESV in comparison to the submaximal treadmill test and therefore the left ventricular function measurements after adenosine infusion should be interpreted carefully and may not represent those acquired after physical exercise. In the gated SPET scans showing ischaemia the post-stress EDV and ESV may be greater and the LVEF lower than at rest.

Pheochromocytomas and paragangliomas (extra-adrenal pheochromocytomas) are relatively rare catecholamine-producing tumors that arise from chromaffin tissue. Radionuclides, such as I-131-meta-iodobenzylguanidine (MIBG), a guanidine derivative, present an imaging modality that has been used for both the diagnosis and staging of chromaffin-cell tumors. Malignant chromaffin-cell tumors account for 10-20% of all cases of chromaffin-cell tumors and show a variable natural history, from a locally invasive indolent tumor to a highly aggressive malignancy. These tumors are best managed by a multidisciplinary team aiming not only at tumor bulk reduction, but also at control of the hypersecretory syndromes resulting from catecholamine excess and maintaining a good quality of life. Surgery with complete resection or debulking of the primary tumor is the treatment of choice, but for disseminated tumors, additional treatment is required. However, systemic chemotherapy has not been shown to be consistently effective, whereas external radiotherapy is mainly reserved for the treatment of localized bony metastases. Pheochromocytomas and paragangliomas that demonstrate positive uptake on a diagnostic I-131/123-MIBG scan can be treated with I-131-MIBG, thus presenting a novel and evolving therapeutic modality in addition to the other traditional therapeutic approaches. In cases with locally aggressive disease, I-131-MIBG therapy is given to complement surgery to help achieve the total eradication of the tumor. In more advanced cases with disseminated disease, I-131-MIBG therapy aims at palliation of symptoms and reduction of tumor function, as well as tumor arrest or even regression after surgery. Treatment with I-131-MIBG is associated with considerable symptomatic and hormonal responses, but fewer patients achieve a tumor response. However, there is stabilization of the disease in the majority with a substantial improvement in the quality of life. 131 I-MIBG therapy is safe and well tolerated with minimal adverse effects, although prolonged follow up is still necessary. Although a randomized, controlled study to access the efficacy of I-131-MIBG treatment and its integration with other forms of therapy is awaited, it remains a valuable alternative or additional therapeutic option to the currently available treatment modalities.