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Biomedical subjects

A G Kettle

Publications and source records attributed to A G Kettle.

At least 19 recordsLinked to original sources

Parathyroid imaging: preoperative localization.

The role of parathyroid localization is as a preoperative localization procedure. This is becoming increasingly important with the trend towards limited surgical approaches. Although there are a variety of methods used to identify the site of parathyroid adenomas, 99mTc sestamibi is at present the agent of choice. Debate continues as to whether imaging is best performed using a subtraction technique or delayed imaging/dual phase technique. There is also discussion as to which collimator to use and whether surgery should be directed by the combined use of ultrasound and radionuclide imaging. These areas are discussed within this review. The technique of choice is a subtraction 99mTc sestamibi scan of the neck using a pinhole collimator. This should be combined with a mediastinal view using a parallel hole collimator. There is sufficient evidence to suggest that combining subtraction imaging with high resolution ultrasound will improve the sensitivity and give greater information to the surgeon.

Humans↗

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.

Aged↗

Radiation exposure of the families of outpatients treated with radioiodine (iodine-131) for hyperthyroidism.

Patients who receive radioiodine (iodine-131) treatment for hyperthyroidism (195-800 MBq) emit radiation and represent a potential hazard to other individuals. Critical groups amongst the public are fellow travellers on the patient's journey home from hospital and members of the patient's family, particularly young children. The dose which members of the public are allowed to receive as a result of a patient's treatment has been reduced in Europe following recently revised recommendations from ICRP. The annual public dose limit is 1 mSv, though adult members of the patient's family are allowed to receive higher doses, with the proviso that a limit of 5 mSv should not be exceeded over 5 years. Unless the doses received during out-patient administration of radioiodine can be demonstrated to comply with these new limits, hospitalisation of patients will be necessary. The radiation doses received by family members (35 adults and 87 children) of patients treated with radioiodine at five UK hospitals were measured using thermoluminescent dosimeters mounted in wrist bands. Families were given advice (according to current practice) from their treatment centre about limiting close contact with the patient for a period of time after treatment. Doses measured over 3-6 weeks were adjusted to give an estimate of values which might have been expected if the dosimeters had been worn indefinitely. Thirty-five passengers accompanying patients home after treatment also recorded the dose received during the journey using electronic (digital) personal dosimeters. For the "adjusted" doses to infinity, 97% of adults complied with a 5-mSv dose limit (range:0.2-5.8 mSv) and 89% of children with a 1-mSv limit (range: 0.2-7.2 mSv). However 6 of 17 children aged 3 years or less had an adjusted dose which exceeded this 1 mSv limit. The dose received by adults during travel was small in comparison with the total dose received. The median travel dose was 0.03 mSv for 1 h travel (range: 2 microSv-0.52 mSv for 1 h of travel time). These data suggest that hyperthyroid patients can continue to be treated with radioiodine on an out-patient basis, if given appropriate radiation protection advice. However, particular consideration needs to be given to children aged 3 years or younger. Admission to hospital is not warranted on radiation protection grounds.

Adolescent↗

Iodine-123 salmon calcitonin, an imaging agent for calcitonin receptors: synthesis, biodistribution, metabolism and dosimetry in humans.

Calcitonin is used to reduce high serum calcium levels in patients with malignancy, and as therapy for osteoporosis and Paget's disease. Receptors for the peptide have been identified in some human cancer cells including those of lung, breast, bone, prostate, and medullary carcinoma of the thyroid, suggesting that an imaging agent for the receptors might be useful in nuclear oncology. A modified chloramine-T method was used to label a pharmaceutical form of salmon calcitonin (SCT) with iodine-123. Labelling can be performed within 5 min including purification, resulting in >95% radiochemical purity and 70% yield. Digestion analysis shows labelling with two iodine atoms on the tyrosine residue. A Chinese hamster ovary cell-based assay showed that the receptor binding and activation were not impaired by the labelling. Biodistribution in mice was similar to that of commercially available mono-iodinated 125I-labelled SCT, kidney being the principal target organ. Evaluation in three patients previously diagnosed as having Paget's disease (injected with 37 MBq [123I]diiodotyrosyl22-SCT, containing less than 4 IU hormone, imaged dynamically up to 0.5 h and at intervals up to 24 h) shows early uptake in liver, kidney and sites of known Paget's disease but not in normal bone, and later uptake in thyroid and stomach. Blood clearance was fitted to a biexponential with half-lives of 3.4-7.4 min and 3-34 h. Radiation dosimetry was estimated using MIRDOSE 3. The highest doses (mean mGy/MBq) were to thyroid (6.8x10(-1)) and kidney (6.0x10(-2)), with a whole-body dose 3.0x10(-2). High performance liquid chromatography analysis revealed that urinary radioactivity was mostly in the form of iodide and diiodotyrosine within minutes of injection, indicating rapid in vivo breakdown. In summary, [123I]diiodotyrosyl22-SCT binds to calcitonin receptors and can image sites of Paget's disease but its imaging potential is not optimal because of rapid breakdown and clearance from target tissues, and an alternative radiolabelling approach is required.

Aged↗

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.

Aged↗

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.

Adult↗

The value of the chest radiograph in reporting aerosol ventilation-perfusion scans.

It has become accepted practice to have a chest radiograph (CXR) available for reference at the time of reporting a ventilation-perfusion (V/Q) scan. We designed a study to determine whether the availability of a CXR altered the interpretation of V/Q scans in our unit. One hundred consecutive V/Q scans were reported with and without reference to a CXR by two radiologists and two nuclear physicians. The V/Q reports were then compared. Our results show that the availability of a CXR has no effect on the V/Q scan report.

Aerosols↗

Can chest X-rays and ventilation/perfusion scans be interpreted reliably from personal computer screens?

A computer-based system is routinely used for home reporting of nuclear medicine scans performed out of hours in our unit. To report ventilation/perfusion scans (V/Q) adequately, chest radiographs are also digitized and transferred to the home personal computer. One hundred consecutive V/Q scans and their corresponding chest X-rays were reported on a personal computer and on a lightbox by two radiologists and two nuclear physicians. This study shows that ventilation/perfusion scans can be reliably reported from computer screen images. The loss of data when chest X-rays are digitized to a 512 x 512 matrix, however, results in considerable misinterpretation and the digitized chest X-ray may, at best, be unhelpful and, at worst, result in an incorrect V/Q scan report.

Diagnostic Errors↗

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.

Bone Neoplasms↗

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.

Adult↗

Ventilation and perfusion lung imaging--which nebulizer?

Three commercially available 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) aerosol delivery nebulizers for lung ventilation imaging were investigated. Two were air-jet systems, 'Optimist' (Medicaid) and 'Microcirrus' (Amersham), and one was an ultrasonic device (Europlus). Altogether, 112 consecutive patients were scanned, 37 using the Optimist, 40 using the Microcirrus and 35 the Europlus. The age mix, FEV1, FVC and PEFR measurements of the patients in each group were similar. Each contained a proportion of patients with poor respiratory function, with PEFR rates ranging from 30 to 582 l min-1 for patients studied with all systems. Ease of use, image quality and cost were evaluated as well as radioactive and microbiological contamination. The Optimist system gave the best combination of image quality and cost, and was associated with the lowest level of radioactive contamination. It also proved the most popular. Airborne contamination for all nebulizers was lower than previously reported and was largely dependent on patient compliance. With poorly compliant patients, the contamination levels are sufficient to warrant an extraction device. There was no evidence of bacterial contamination of the nebulizers or tubing on repeated use over 5 days.

Forced Expiratory Volume↗

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.

Computer Communication Networks↗

Intraoperative localization of recurrent medullary carcinoma of the thyroid using indium-111 pentetreotide and a nuclear surgical probe.

A patient with recurrent medullary thyroid cancer in the neck in whom previous surgery for recurrence had been undertaken with only partial success had the diseased tissue localized preoperatively by indium-111 pentetreotide. Scanning with technetium-99m V dimercaptosuccinic acid and iodine-123 metaiodobenzylguanidine failed to localize the tumor. Utilization of a nuclear surgical probe after preoperative 111In pentetreotide allowed accurate surgical localization of the tumour tissue.

Adult↗