Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease.

AIM: To establish whether bone disease is present at diagnosis in inflammatory bowel disease and to identify contributory metabolic abnormalities. METHODS: Newly diagnosed patients with inflammatory bowel disease (19 males, 15 females; mean age, 44 years; range, 17-79 years; 23 ulcerative colitis, 11 Crohn's disease) were compared against standard reference ranges and a control group with irritable bowel syndrome (eight males, 10 females; mean age, 40 years; range, 19-64 years). Bone mineral density (g/cm2, dual-energy X-ray absorptiometry: lumbar spine and femoral neck) and biochemical bone markers were measured. RESULTS: Femoral neck bone mineral density, T- and Z-scores (mean +/- s.d., respectively) were lower in inflammatory bowel disease patients than in irritable bowel syndrome controls (0.78 +/- 0.12 vs. 0.90 +/- 0.16, P = 0.0046; - 0.88 +/- 0.92 vs. 0.12 +/- 1.17, P = 0.0018; - 0.30 +/- 0.89 vs. 0.61 +/- 1.10, P = 0.0030). Lumbar spine bone mineral density and T-scores were also significantly lower in patients than controls (0.98 +/- 0.15 vs. 1.08 +/- 0.13, P = 0.0342; - 1.05 +/- 1.39 vs. - 0.14 +/- 1.19, P = 0.0304). Compared with controls, the urinary deoxypyridinoline : creatinine ratio was increased (7.66 vs. 5.70 nmol/mmol, P = 0.0163) and serum 25-hydroxy vitamin D was decreased (18.7 vs. 28.5 micro g/L, P = 0.0016); plasma osteocalcin and serum parathyroid hormone did not differ (P > 0.05). CONCLUSIONS: The bone mineral density is reduced at diagnosis, prior to corticosteroid treatment, in both Crohn's disease and ulcerative colitis. Our data suggest that this is attributable to increased resorption rather than decreased bone formation.

Imaging of abdominal infection using 99m Tc stannous fluoride colloid labelled leukocytes.

Radiolabelling of leukocytes using labelled phagocytosed technetium-99m (99mTc) colloidal radiopharmaceuticals has been reported as a method for imaging infection. This in vivo study compares the use of leukocytes labelled using 99mTc stannous fluoride colloid with leukocytes labelled using indium-111 (111In) oxinate. A total of 26 patients (10 male, 16 female; mean age 52 years, range 23-88 years) referred for the investigation of possible infection were studied using both leukocyte labelling methods simultaneously. Images were acquired 4h and 24h after re-injection of the labelled cells. The images were evaluated qualitatively by two nuclear medicine physicians. The results show a high degree of concordance between the techniques: 11 of the 28 images showed a focus of leukocyte accumulation with both techniques at 24h, and 13 out of 28 showed a normal appearance at 24h with both methods. In four cases the results were discordant; the 99mTc stannous fluoride colloid labelled leukocytes gave a false positive appearance at 24h in three patients and a false negative in one. In conclusion, colloid labelling of leukocytes offers a sensitive method for the detection of infective foci coupled with the high resolution imaging offered by 99mTc. It has the advantage over other in vitro labelling methods of being a simpler, non-labour-intensive procedure employing whole blood, and its use should be considered by departments that have limited facilities for in vitro leukocyte labelling.

99mTc(V)DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with prostate cancer metastatic to bone.

Rhenium-188 dimercaptosuccinic acid complex [188Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent 99mTc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if 99mTc(V)DMSA could be used to predict tumour and kidney retention of 188Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of 99mTc(V)DMSA and 188Re(V)DMSA. This would determine whether a scan with 99mTc(V) DMSA could be used to identify patients for whom 188Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in 188Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent 99mTc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq 99mTc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq 188Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the 188Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on 188Re scans than on 99mTc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for 188Re than for 99mTc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between 99mTc and 188Re scans, and kidney-to-background ratios on 188Re scans were not higher than on 99mTc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus 99mTc(V)DMSA scans are predictive of 188Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for 188Re(V)DMSA treatment.

(99m)Tc(V)DMSA quantitatively predicts (188)Re(V)DMSA distribution in patients with prostate cancer metastatic to bone.

Rhenium-188 dimercaptosuccinic acid complex [(188)Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent (99m)Tc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if (99m)Tc(V)DMSA could be used to predict tumour and kidney retention of (188)Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of (99m)Tc(V)DMSA and (188)Re(V)DMSA. This would determine whether a scan with (99m)Tc(V)DMSA could be used to identify patients for whom (188)Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in (188)Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent (99m)Tc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq (99m)Tc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq (188)Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the (188)Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on (188)Re scans than on (99m)Tc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for (188)Re than for (99m)Tc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between (99m)Tc and (188)Re scans, and kidney-to-background ratios on (188)Re scans were not higher than on (99m)Tc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus (99m)Tc(V)DMSA scans are predictive of (188)Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for (188)Re(V)DMSA treatment.

A one-hour walk-in service for wrist trauma imaging.

We investigated the feasibility of rapid imaging of wrist trauma following casualty presentation and any subsequent effect on image quality and interpretability. All patients referred for wrist imaging were injected with 370 MBq 99Tcm-hydroxymethyl diphosphonate (HDP) and imaged 1, 2 and 3 h later. Palmar images were acquired on a 256 x 256 x 16 matrix using a high-resolution collimator, 140 keV photopeak and a 20% window. The images were scored qualitatively by four qualified observers in three categories: image quality, lesion detection and lesion localization. Statistical analysis indicated a significant improvement in scan quality with time, the mean difference (+/- standard error of the mean) between the 1 and 3 h scans being 0.81 +/- 0.07 (P = 0.001). No significant differences were seen in lesion detection (0.05 +/- 0.08; P = 0.51) or localization (0.14 +/- 0.08; P = 0.10). We conclude that imaging of wrist trauma is possible as early as 1 h post-injection of 99Tcm-HDP, although negative studies at 1 h require a 3 h image to maintain diagnostic accuracy.

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma.

The management of 38 consecutive patients with differentiated thyroid carcinoma in the period 1991-1996, who each received at least one therapy dose of iodine-131, was reviewed, looking in particular at those in whom anterior mediastinal uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity was noted in ten patients. On the basis of clinical follow-up, thyroglobulin measurement and radiological and other scintigraphic imaging, in nine of the ten patients the anterior mediastinal activity was attributed to physiological thymic uptake. Of those nine, all were under 50 years of age; seven were considered disease free, one had residual disease in the neck and one had distant metastases. Physiological uptake by the thymus was more prominent on the 7-day scans and in patients with low tumour volumes. For appropriate patient management it is essential to recognise that physiological uptake of 131I by the thymus in patients under 50 years of age is a potential cause of false-positive therapy scans.

Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies.

Pentavalent rhenium-188 dimercaptosuccinic acid [188Re(V)DMSA] is a beta-emitting analogue of 99mTc(V)DMSA, a tracer that is taken up in a variety of tumours and bone metastases. The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of 188Re in mice was determined 2 h after injection of 3 MBq 188Re(V)DMSA prepared from eluate from a 188W/188Re generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases confirmed with a standard 99mTc-hydroxymethylene diphosphonate (99mTc-HDP) scan, were given 370 MBq 188Re(V)DMSA and imaged at 3 h and 24 h using the 155-keV gamma-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of 188Re. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice, 188Re(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongly reminiscent of 99mTc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of 188Re in any chemical form other than 188Re(V)DMSA up to 24 h. In conclusion, 188Re(V)DMSA and its 186Re analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate 99mTc(V)DMSA.

Drug therapy alternatives in the treatment of thyroid cancer.

Therapy of thyroid cancers is based on the removal of the primary disease by surgery, replacement of the hormonal deficiencies and subsequent therapy of the recurrent and metastatic disease. The metabolic characteristics of many thyroid tumors mean that radionuclide techniques have been used in the identification of sites of tumour and their subsequent therapy. Differentiated thyroid cancers, papillary, follicular and mixed papillary follicular, are treated by surgery--usually a total or subtotal thyroidectomy. Postoperatively, patients have thyroxine as a replacement therapy and to suppress thyroid-stimulating hormone production. Radioiodine therapy is often given to ablate the thyroid remnant. This allows (a) adequate follow-up of patients using thyroglobulin measurements and assessment scans as necessary, and (b) further therapy with radioiodine for metastatic disease. Patients with a short effective half-life of radioiodide may require higher activities or pharmacological methods of prolonging the retention half-times of iodine. The use of chemotherapy in this group of tumors is limited and at best provides palliation. The overall prognosis is good for differentiated thyroid cancer; papillary carcinomas have an 80 to 90% 10-year survival, whereas follicular tumors are associated with a 65 to 75% 10-year survival. Medullary carcinomas may be sporadic or familial, and some of the latter form part of a multiple endocrine neoplasia syndrome (MEN). Primary treatment is surgery, and total thyroidectomy is usually recommended since tumours are often multifocal. The use of radiolabelled metaiodobenzylguanidine (MIBG) and 111In octreotide as potential therapeutic agents has been explored and may be potentially useful in palliative care. Chemotherapy is of limited benefit. The 10-year survival for medullary carcinomas is 60 to 70%. Anaplastic tumours of the thyroid are usually aggressive, with a high mortality. Treatment is palliative by surgical debulking; some patients may benefit from local radiotherapy or occasionally chemotherapy. The use of therapeutic doses of radionuclides is well tolerated, although it may be associated with a variety of mostly transient adverse effects, including gastritis, thyroiditis and sialadenitis. Therapy with high activities of radioiodine require radiation protection precautions. Despite retreatment with radioiodine there appear to be no long term effects on the fertility of patients, and healthy children are born to women receiving this treatment. 131I remains perhaps the most specific cancer therapy available today and has few adverse effects. It is difficult to see any marked improvement being developed for differentiated thyroid cancer, with the possible exception of targeted gene therapy.

Pentavalent 99Tcm-DMSA imaging in patients with bone metastases.

Pentavalent 99Tcm-dimercaptosuccinic acid (99Tcm-(V)DMSA) has an established role in imaging medullary thyroid carcinoma. There have been case reports of uptake in bone metastases. Our aims were to compare 99Tcm-(V)DMSA with 99Tcm-hydroxymethylene diphosphonate (99Tcm-HDP) in bone metastases, to assess its value in imaging of bone metastases, and to assess the prospects of the beta-emitting analogues 186/188Re-(V)DMSA as palliative agents for painful bone metastases. Ten patients confirmed by a 99Tcm-HDP bone scan to have bone metastases secondary to carcinoma of the prostate, lung or breast were injected with 99Tcm-(V)DMSA (600 MBq). Whole-body scans acquired at 3 and 24 h were compared with the 99Tcm-HDP bone scans. 99Tcm-(V)DMSA showed high soft tissue background, kidney retention and avid uptake in most bone metastases: 86% of bone lesions identified on bone scans were detected with 99Tcm-(V)DMSA. The lesion-to-normal ratios were comparable to or lower than those for 99Tcm-HDP at 3 h, but increased by 24 h. Instances of abnormal uptake in liver, primary lung tumour, lymph nodes and pleural effusion were observed. We conclude that 99Tcm-(V)DMSA is a tracer for bone metastases (with lower sensitivity than 99Tcm-HDP) and soft tissue tumours. If 186/188Re-(V)DMSA behave similarly, they may find use in therapy for soft tissue tumours and bony metastases.

The effects of standardization and reference values on patient classification for spine and femur dual-energy X-ray absorptiometry.

The effect of two methods for standardizing dual-energy X-ray absorptiometry (DXA) measurements on patient classification by the T-score has been determined for a group of over 2000 patients. The methods proposed by the International DXA Standardization Committee and the European Community's COMAC-BME group were used in conjunction with young reference data from the major DXA manufacturers, the COMAC-BME group and the third US National Health and Nutrition Examination Survey (NHANES III). The two standardization techniques produced dissimilar classifications as measured by the kappa statistic (kappa = 0.34-0.90), especially for the femoral neck, with up to 24.3% of patients reclassified from osteopenic to normal and 18.6% reclassified from osteoporotic to osteopenic when the standardization method was changed. Considering the effects of both reference data and standardization techniques together, there was a wide variation of patient classification, with the number of patients classified as osteoporotic varying from 9.6% to 21.1% for the postero-anterior spine L2-4 region and from 2.3% to 27.6% for the femoral neck. The agreement between different classifications ranged widely, from very poor to excellent (kappa = 0.02-0.98). The creation of standardized reference data must be an important priority in order to harmonize patient management using standardized BMD measurements. The choice of standardization technique, however, must be addressed in light of the results presented here.

Assessment of changes in dual-energy X-ray absorptiometry performance following a system upgrade.

System upgrades are a constant feature of many highly technical specialties and are normally assumed to have a negligible effect on patient data. We report on the assessment of an upgrade made to a Norland XR-26 dual-energy X-ray absorptiometry (DXA) system. The upgraded version (2.3) consisted of new hip positioning aids, hip image analysis software and updates to the normal ranges. Measurements of femoral neck and trochanteric bone mineral density correlated well between versions (r = 0.969 and r = 0.971), those for femoral neck and trochanteric bone mineral content less well (r = 0.956 and r = 0.911), and Ward's triangle values and femoral neck area measurements were poorly correlated (r = 0.719-0.881). The upgrade was claimed to improve precision while reducing analysis and imaging time. Improved precision was not demonstrated, with good precision found both before and after the upgrade. Correlation between femoral neck Z-scores were good for the European normal range (r = 0.970), but unacceptable for the UK range (r = 0.769). These correlations were not close enough to allow patients scanned with the old version to be followed up with scans using the upgrade. The upgrade was, however, preferred for new attenders because of the improved speed and automation of hip analysis, without loss of precision. The most important implication in terms of patient management was the change made to the UK normal range, which had a very large effect on the number of patients deemed to be at risk from osteoporosis. It is essential that any upgrade introduced to an existing DXA system is carefully evaluated, since it may affect system performance and patient results.

Radiation dose rates from patients receiving iodine-131 therapy for carcinoma of the thyroid.

Patients treated with radioiodine present a radiation hazard and precautions are necessary to limit the radiation dose to family members, nursing staff and members of the public. The precautions advised are usually based on instantaneous dose rates or iodine retention and do not take into account the time spent in close proximity with a patient. We have combined whole-body dose rate measurements taken from 86 thyroid cancer patients after radioiodine administration with published data on nursing and social contact times to calculate the cumulative dose that may be received by an individual in contact with a patient. These dose estimates have been used to calculate restrictions to patients behaviour to limit received doses to less than 1 mSv. We have also measured urinary iodide excretion in 19 patients to estimate the potential risk from the discharge of radioiodide into the domestic drainage system. The dose rate decay was biexponential for patients receiving radioiodine to ablate the thyroid after surgery (the ablation group, A) and monoexponential for these receiving subsequent treatments for residual or recurrent disease (the follow-up group, FU). The faster clearance in the follow-up patients generally resulted in less stringent restrictions than those advised for ablation patients. For typical activities of 1850 MBq for the ablation patients and 3700 MBq or 7400 MBq for the follow-up patients, the following restrictions were advised. Patients could travel in a private car for up to 8h on the day of treatment (for an administered activity of 1850 MBq in group A) or 4 and 2h (for activities of 3700 or 7400 MBq in group FU) respectively. Patients should remain off work for 3 days (1850 MBq/group A) or 2 days (up to 7400 MBq/group FU). Partners should avoid close contact and sleep apart for 16 days (1850 MBq/group A) or 4-5 days (3700 or 7400 MBq/group FU). Contact with children should be restricted according to their age, ranging from 16 days (1850 MBq/group A) or 4-5 days (3700 or 7400 MBq in group FU) for younger children, down to 10 days (1850 MBq/group A) or 4 days (up to 7400 MBq/group FU) for older children. The cumulative dose to nursing staff for the week after treatment was dependent on patient mobility and was estimated at 0.08 mSv for a self-caring patient to 6.3 mSv for a totally helpless patient (1840 MBq/group A). Corresponding doses to nurses looking after patients in group FU were 0.18-12.3 mSv (3700 MBq) or 0.36-24.6 mSv (7400 MBq). Sensible guidelines can be derived to limit the dose received by members of the public and staff who may come into contact with cancer patient treated with radioiodine to less than 1 mSv. The rapid clearance of radioiodine in patients treated on one or more than one occasion means that therapy could be administered at home to selected patients with suitable domestic circumstances. In most cases the restriction times, despite the high administered activities, are less than those for patients treated for thyrotoxicosis. The concentration of radioiodide in domestic drainage systems should not pose a significant risk.

A survey of dual-energy X-ray absorptiometry (DEXA) normal reference ranges used within the UK and their effect on patient classification.

Differences between dual-energy X-ray absorptiometry (DEXA) normal ranges can lead to patients being characterized as osteoporotic using one range and normal using another. To investigate the diversity of normal ranges used within the UK, a survey of all DEXA sites was carried out with a 60.6% response rate. The effect of the different ranges was evaluated by translating each range to an equivalent range for a Norland XR-26 system and applying the ranges to stratify a representative sample of over 1000 patients into grades of bone density based on percentages of age-matched mean BMD, Z-scores and T-scores. The effect of femoral neck and P/A spine L2-L4 regions was considered both separately and jointly. Large differences between the normal ranges were apparent, which resulted in the classification of the number of patients with a Z-score of less than -2.0 varying by a factor of more than 20 for the femoral neck and more than 3 for the spine. The number of patients defined as osteoporotic by a T-score less than -2.5 varied from none to over one-third of patients for the hip and by a factor of almost 3 for the spine. The exclusion criteria used for construction of the normal ranges varied markedly with none constructed using population-based sampling. Smoothing of normal ranges was carried out by DEXA manufacturers, while local normal ranges made use of raw unprocessed data. There is reason to question the validity of such processing. We recommend the construction of a unified UK normal range applicable to all UK DEXA systems in order to harmonize patient management and care.

Home reporting for the nuclear clinician?

The computer-based 'home office' is becoming a widely accepted mode of operation for modern businesses. It is implausible to believe that a nuclear medicine department can be covered permanently at a distance by a single physician, but it should be possible to provide cover for colleagues during sickness or at night or weekends. We have used a 486 PC with a high-resolution screen and software provided by LINK Medical Ltd to obtain images from hospital sites using a modem link to ADAC, Bartec and Nuclear Diagnostic SUN workstations. The data were transferred via standard telephone lines to the homes of two of the authors. During a trial period lasting several months, 60 lung scans, 20 bone scans, 1 gastrointestinal bleeding study, 4 leukocyte scans, 5 bone tomograms, 9 renograms, 6 myocardial perfusion tomograms and 2 gated cardiac studies were transferred. The system allowed transfer of a 128 x 128 eight-view lung scan to be completed in approximately 2 min. The program on the PC allowed alteration of individual image contrast, image rotation, cine display and a variety of colour scales to enhance image interpretation. A system to transfer chest X-rays has been developed and typical transfer times are approximately 3.5 min. Within the viewing protocol on the PC, a reporting window was available with the ability to fax the report directly to the hospital. The system allowed consultants who live at a distance from their nuclear medicine departments to provide cover and is now used as an integral part of our out-of-hours service. The system also allows cover of satellite units or to provide cover for junior staff at night or weekends.