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Biomedical subjects

V R McCready

Publications and source records attributed to V R McCready.

At least 91 records · Page 5Linked to original sources

The effect of chelating agents on the distribution of monoclonal antibodies in mice.

The potential for altering the biodistribution of radiolabel from gallium- and indium-labeled mouse monoclonal antibodies was investigated in mice using metal chelating agents. The chelating agents used were desferrioxamine (DFO), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-di (O-hydroxyphenylacetic acid) (EDHPA), and 2,2' dipyridyl (DIPY). The mouse monoclonal antibody LICR-LON-M8 was labeled with 111In after conjugation to DTPA, and with 67Ga after conjugation to DFO. All the chelating agents except DIPY altered the biodistribution of [67Ga]citrate and [111In]citrate but did not affect the 48-hr tissue uptake of label from [111In]DTPA-M8 or [67Ga]DFO-M8, confirming the in vivo stability of the antibody conjugates. Label fixed in the tissues was inaccessible to the chelating agents, indicating that they will not be suitable for reducing the high background liver radioactivity in patients undergoing scanning with indium-labeled antibodies.

2,2'-Dipyridyl↗

The measurement of radiation doses from P32 chromic phosphate therapy of the peritoneum using SPECT.

Single photon emission computed tomography (SPECT) has been shown to be of value in estimating the radiation dose to the peritoneum from 32P therapy. Simple dosimetry calculations, assuming uniform irradiation of tissue, indicate that radiation doses of approximately 40 Gy to the peritoneal surface are achieved. However, the images show that the radionuclide distribution is non-uniform, giving rise to radiation dose variations of at least a factor of 10.

Chromium↗

Low-dose 131I in treatment of Graves' disease.

One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 4 1/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome.

Adult↗

Low-dose radioiodine given six-monthly in Graves' disease.

Experience using low-dose radioiodine given six-monthly instead of yearly in hyperthyroid patients with Graves' disease is reported. One hundred and thirty-five patients have been treated over a three-year period with 74 MBq (2 mCi) doses of 131I. Thirty-eight percent were controlled with a single dose. Those patients requiring more than one dose were treated with a further 74 MBq (2 mCi) 131I at six-monthly intervals until euthyroid. Using this approach, 46% were euthyroid one year after starting treatment, and 75% were euthyroid at two years. The incidence of hypothyroidism following treatment was 2.2% at one year, with a yearly incidence thereafter of 4-6%. Six-monthly scheduling of low-dose radioiodine in Graves' disease can reduce the time taken to become euthyroid, compared with conventional yearly low-dose treatments. Further follow up is required to confirm the present low incidence of hypothyroidism following treatment.

Aged↗

The appearance of the pyramidal lobe on thyroid scintigraphy.

The standard nuclear medicine textbooks describe the pyramidal lobe of the thyroid as arising from the upper part of the thyroid lobes. Anatomy and surgical texts however describe it as a thyroglossal tract remnant and state that it arises from the isthmus. Review of 150 thyroid scintigrams confirms that on scintigraphy the pyramidal lobe does appear to originate from the upper pole. We have used single photon emission tomography to demonstrate the true origin of the pyramidal lobe by removing overlying thyroid tissue. We suggest that the pyramidal lobe arises from the isthmus and the appearances on scintigraphy are due to the lower part of the lobe being obscured behind the main thyroid lobe.

Humans↗

Radioiodine treatment of metastatic thyroid carcinoma: the Royal Marsden Hospital experience.

The case records of 235 patients who were treated for differentiated thyroid cancer between 1949 and 1981 were reviewed. Forty-two (18%) had distant metastatic spread outside the neck and received radioiodine (131I) therapy. In cases where the distant spread was confined to the lungs, 54% of patients were alive, free of disease, 10 years after 131I treatment was started. By contrast, no patient with skeletal involvement has survived for 10 years and only one for five years after treatment. A variety of cytotoxic drugs has been tried on an ad hoc basis with no notable success. One patient developed preleukaemia three months after completion of 131I treatment, but no other serious side effects were observed. Factors that influence the behaviour of metastatic thyroid carcinoma are discussed and a possible revised approach to 131I therapy is suggested in the light of these findings.

Adenocarcinoma↗

A clinical evaluation of a prototype positron camera for longitudinal emission tomography.

A multiwire proportional-chamber positron camera, developed at the Rutherford Laboratory, has been evaluated at The Royal Marsden Hospital. The prototype camera consists of two opposing 30 X 30 cm2 chambers. Longitudinal tomograms of a positron-emitting radioactive distribution placed between the detectors are obtained via back-projection and 2D-deconvolution. Due to the limited stereoscopic angle achieved with stationary detectors, only five planes parallel to the detector faces are reconstructed. A selection of images is presented of phantoms using 68Ga and of patients using 18F, 18F fluorodeoxyglucose and Na124I, to illustrate the tomographic performance of the positron camera. A comparison between back-projected and deconvoluted images shows that the 2D-deconvolution process, which includes filtration of image noise, successfully removes the background due to scattered photons. The spatial resolution achieved depends on the half-height frequency cut-off used in the filtering process, and this parameter was chosen according to the count density in the back-projected images. A qualitative visual comparison was made between the positron images and equivalent single photon studies on the same patient. The results justify further development of this new detector, especially for use with generator-produced positron-emitting radionuclides. Three-dimensional deconvolution resulted in improved tomographic performance for phantom data, but was less successful for patient data. These problems associated with limited-angle tomography will be overcome by multi-view acquisition. This study has shown that a relatively low-cost positron imaging system can be used for routine organ imaging. Further developments in hardware and software should yield images which are superior to those from single-photon planar or tomographic studies.

Bone Marrow↗

Location of metastatic breast carcinoma by a monoclonal antibody chelate labelled with indium-111.

The ability of a radiolabelled monoclonal antibody, LICR-LON-M8 (M8), to locate metastatic breast carcinomas has been investigated. The scans generated by M8, either when labelled with radioiodine, or when conjugated with diethylenetriamine-pentaacetic acid (DTPA) and labelled with radioactive indium (111In), have been compared with X-rays and 99mTc-methyl diphosphonate (MDP) bone scans. All 10 patients with skeletal metastases had positive 111In-DTPA-M8 scans and the overall correlation with X-rays and MDP scans was good but varied with the region studied. By contrast, radioiodinated M8 did not detect metastases at any site. The discrepancies between 111In-DTPA-M8 images and conventional techniques may be related to the different stages in the evolution and development of the lesion at which the various techniques detect bone metastases.

Antibodies, Monoclonal↗

Detection of breast carcinoma metastases in bone: relative merits of X-rays and skeletal scintigraphy.

Of 1116 patients receiving primary treatment for breast carcinoma at the Royal Marsden Hospital since 1976, 651 had an abnormal bone scintigram either at primary diagnosis (378) or on subsequent follow-up (273) and 167 developed radiographically detectable bone metastases (21 at the time of primary diagnosis). Comparison of bone scintigrams and X-rays showed that scintigraphy was an inaccurate localiser of existing radiographic detectable metastases. If X-rays alone are used to detect bone metastases a limited examination with five plates will detect metastases with 92% accuracy. After primary surgery, routine X-ray screening for bone metastases is not necessary since it is possible to identify patients at risk on the basis of clinical examination, chest X-ray, and serum alkaline phosphatase and gamma-glutamyl transpeptidase levels.

Alkaline Phosphatase↗

Assessment of response of bone metastases to systemic treatment in patients with breast cancer.

Seventy-one patients with breast cancer and bone metastases, together with other assessable sites of disease, were monitored by radiologic skeletal survey, bone scanning, pain charts, bone marrow aspirate, serum calcium, alkaline phosphatase and urine hydroxyproline/creatinine ratio. On the basis of UICC criteria of response in nonosseous sites, 37 were classed as responders and 34 as nonresponders. Responding patients with osteolytic disease frequently showed sclerosis, but only at 6-8 months, whereas patients with mixed lytic/sclerotic or sclerotic metastases frequently showed no change or further sclerosis. Nonresponders most frequently showed progressive lysis. Bone scanning showed clear evidence of improvement or deterioration in 7/21 responders and 8/23 nonresponders who showed no definite evidence of progression or response on skeletal radiography. Pain assessment was also useful in these patients. Neither the bone marrow aspirate nor other biochemical tests were useful in assessing response to therapy. This study concludes that bone scanning and pain assessment are both useful in assessment of response of bone metastases to treatment in some patients and incorporation into a standard criteria of response is recommended.

Alkaline Phosphatase↗

Role of ultrasound in the management of ovarian carcinoma.

The ultrasound findings of the pelvis, upper abdomen and peritoneal cavity were correlated with second-look laparotomy in 85 patients with Stage III or Stage IV ovarian carcinoma. High values of accuracy were obtained for the pelvis (90%) and liver (91%) but ultrasound was insensitive to peritoneal disease unless ascites was present.

Adult↗

The limitations of the dual radionuclide subtraction technique for the external detection of tumours by radioiodine-labelled antibodies.

A dual radionuclide subtraction technique for external detection of tumours has been evaluated to determine the viability of the method for use with radioisotope labelled antibodies. A number of external scintigraphic investigations have been carried out with 131I-labelled antibodies to carcinoembryonic antigen (CEA). The investigations were performed on patients with metastatic disease known to produce CEA. The dual radionuclide subtraction technique was used to account for the blood and tissue background. The 131I-labelled antibodies were found to localise in the metastatic lesions, but the subtraction technique using 99Tcm-labelled HSA and pertechnetate gave ambiguous results, which included the production of artefacts. The ambiguities noted in the clinical results were substantiated by experimental data, which highlight the unreliability of this technique.

Antibodies, Neoplasm↗

A comparison between 180 degrees and 360 degrees data reconstruction in single photon emission computed tomography of the liver and spleen.

Single photon emission computed tomography (SPECT) of the liver and spleen has been studied using a GE400T/STAR rotating gamma camera/computer system. We have compared section image contrast, in both phantom and patient studies, produced by 180 degrees and 360 degrees reconstructions of data from a full 360 degrees data acquisition. There is little difference in overall image quality between the two reconstruction modalities. Quantitatively, however, appropriate 180 degrees reconstructions significantly improve lesion contrast in both organs by as much as a factor of two. In all cases studied, the values of image contrast achieved when the 180 degrees arc of reconstruction was centred about the region of interest were higher than the values obtained from the 360 degrees reconstructions. These results are shown to be independent of the corrections made for photon attenuation. Clinically this technique may prove useful in clarifying the presence or absence of disease, particularly in equivocal cases where lesions have poor contrast or are small in size. An extended clinical trial of the technique is now in progress.

Adult↗

Ultrasonography of Hodgkin's disease in the liver and spleen.

Ultrasound findings of 39 spleens and 68 livers in which histology was obtained at laparotomy or autopsy within a month of the examination and four livers in which abnormalities were found clinically by other methods during long-term follow-up were reviewed to evaluate the various sonographic appearances and the accuracy in detecting involvement of the spleen and liver. Only one out of 17 positive spleens had definite ultrasonic focal lesions. Not only small splenic Hodgkin's foci but also larger ones were overlooked. Of 10 positive livers, six showed diffuse inhomogeneity throughout the liver, two showed multiple, well-defined, echo-poor lesions but two showed no significant ultrasonic abnormality even in retrospect. No correlation was found between the type of Hodgkin's disease and the ultrasonic appearance of involved livers. Ultrasonic examination, however, could differentiate other liver abnormalities, such as fatty changes, a cyst and a thrombosed haemangioma from infiltration of Hodgkin's disease. In one case, splenic lesions became echogenic following-chemotherapy.

Adolescent↗