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Biomedical subjects

V R McCready

Publications and source records attributed to V R McCready.

At least 55 records · Page 3Linked to original sources
PubMed1993

Radioimmunolocalisation in breast cancer using the gene product of c-erbB2 as the target antigen.

Lymph node status is still the single most important prognostic factor in breast cancer. Axillary surgery remains the only reliable means of providing this information. This pilot study evaluates using a highly specific radiolabelled monoclonal antibody to provide equivalent information by a non-invasive technique. After optimisation of labelling conditions, our first antibody, ICR12 (against the gene product of c-erbB-2) was evaluated in a mouse model system. Twenty-four hours post i.v. injection the mice were killed and their organs, blood and tumours harvested for counting. Tumour localisation was four times greater than that into normal tissues, reaching 20% injected dose per gram of tumour. Eight patients have had this Tc99m-ICR12. Patient selection was by immunocytochemical staining of fine needle aspirates from the patient's own breast cancer. After intravenous administration of the immunoconjugate, tomographic images were obtained at 24 h. These results were compared to the subsequent histopathological examinations. Three patients acted as normal controls, one patient was negative due to inappropriate sampling, and two patients had strong membrane staining and provided excellent tumour localisation to both breast primary and regional node metastases. A further two patients only had moderate antigen expression on staining and did not localise well. The good performance of this radiolabelled antibody with patients that strongly stain for the antigen encourages the development of this system as both a method of staging breast cancer and a potential means of immunotherapy in this subgroup of patients.

Adult↗
PubMed1993

The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study.

BACKGROUND: 5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. PATIENTS AND METHODS: Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. RESULTS: Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007). CONCLUSIONS: MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Cellular versus vascular rejection in transplant kidneys. Correlation of radionuclide and Doppler studies with histology.

The presence of two distinct subtypes of renal allograft rejection are well documented by histological studies. The differentiation between vascular rejection (VR) and cellular rejection (CR) is essential for proper management by avoiding the need for unnecessary and potentially harmful immunosuppressive treatment of VR. A histological pattern with features that are similar and confusable with some cases of rejection may be seen in cyclosporin A toxicity (CyT). To evaluate the efficiency of Guy's perfusion index (GPI) and the Doppler pulsatility index (DPI) in differentiating these two histological subtypes, a prospective study was designed in which a total of 140 radionuclide tests and 133 ultrasounds scans performed on the same day on 58 patients during the first 3 months post-transplant were analysed, and the results correlated with the histological findings of 84 renal biopsies. Results show that the GPI had a sensitivity of 86.5% and a specificity of 94% in differentiating VR and CyT from CR, while the DPI had values of 83% and 69%, respectively. Chi-squared analysis showed a higher significant association between the GPI and histology (P < 0.0001) compared to that of the DPI and histology (P < 0.005), while Youden's index (J) showed a significant difference (P < 0.05) between GPI and DPI. It is concluded that GPI is more sensitive and specific than DPI in differentiating transplants that are well perfused from those with poor perfusion (VR and CyT).

Adult↗
PubMed1992

Anatomically derived attenuation coefficients for use in quantitative single photon emission tomography studies of the thorax.

Elimination of errors due to poor attenuation correction is an essential part of any quantitative single photon emission tomography (SPET) technique. Attenuation coefficients (mu Tc) for use in attenuation correction of SPET data were determined using technetium 99m and cobalt 57 flood sources and using topographical information obtained from computed tomography (CT) scans and magnetic resonance (MR) images. In patients with carcinoma of the bronchus, the mean attenuation coefficient for 99mTc was 0.096 cm-1 when determined across a transverse section of the thorax at the level of the tumour by means of a 57Co flood source (13 patients) and 0.093 and 0.074 cm-1 as determined from CT scans for points in the centre of the tumour and contralateral normal lung, respectively (21 patients). In 18 patients with breast tumours, the mean attenuation coefficient for 99mTc was 0.110 and 0.076 cm-1 when determined from MRI cross-sections for points in the centre of the tumour and normal contralateral lung, respectively. This indicates significant overcorrection for attenuation when the conventional value of 0.12 cm-1 is used. A value in the range 0.08-0.09 cm-1 would be more appropriate for SPET studies of the thorax. An alternative approach to quantitative region of interest (ROI) analysis is to perform attenuation correction appropriate to the centre of each ROI (using topographical information derived from CT or MRI) on non-attenuation-corrected reconstructions.

Breast Neoplasms↗
PubMed1992

A comparison of gallium-67 single photon emission computed tomography and computed tomography in mediastinal Hodgkin's disease.

The role of gallium-67 single photon emission computed tomography (Ga-67 SPECT) in the assessment of mediastinal Hodgkin's disease was evaluated prospectively. Ga-67 SPECT and computed tomography (CT) were compared and correlated with clinical findings at initial presentation in 30 patients, 6 weeks after treatment, and 6 months later in 20 of the 30 patients. At initial presentation, active disease was detected on both imaging modalities on all occasions. 6 weeks after treatment CT showed residual mediastinal abnormality in 7 patients, whereas Ga-67 SPECT showed abnormal mediastinal tracer uptake in 3 patients. 6 months later CT showed residual mediastinal abnormality in 5 patients whereas all the Ga-67 SPECT studies were negative. Ga-67 SPECT imaging is a useful tool in assessing response to therapy in mediastinal Hodgkin's disease.

Adult↗
PubMed1991

The effect of intra-tumour heterogeneity on the distribution of phosphorus-containing metabolites within human breast tumours: an in vitro study using 31P NMR spectroscopy.

The concentration of phosphorus-containing metabolites was determined in extracts of multiple samples from six human breast tumours and in samples from normal and inflamed breast tissue. The degree of lymphoid infiltrate, necrotic fraction and tumour cell and normal tissue fraction were determined on sections taken from each of the tumour samples. In four of the tumours there was a very high degree of variation between samples in the absolute concentration of metabolites. Three of these tumours showed a high degree of intra-tumour variation in the distribution of tumour cells and of normal tissue. The other two tumours were relatively homogeneous with respect to both tumour cellularity and the distribution of phosphorus-containing metabolites. Samples from normal breast tissue was found to contain only low concentrations of phosphorus-containing metabolites. However one of the inflamed samples, which consisted predominantly of macrophages, contained high levels of such compounds. The effect of time delay between resection and freezing on the levels of metabolites in human breast tumours was also examined.

Breast↗
PubMed1991

A comparison of in vivo and in vitro 31P NMR spectra from human breast tumours: variations in phospholipid metabolism.

An in vivo 31P NMR spectrum was obtained from each of four human breast tumours. The phosphomonoester and phosphodiester region of each spectrum consisted of a broad peak. Chemical extracts from samples of each of the tumours obtained at resection were examined on a high field strength NMR system. The phosphomonoester region in the spectrum from each extract resolved into three peaks consisting of phosphocholine, phosphoethanolamine and a nucleoside monophosphate. The phosphodiester region resolved into two components, glycerophosphorylcholine and glycerophosphorylethanolamine. Comparing the in vivo and in vitro data from each tumour showed that the contribution of phosphodiester was much lower in the in vitro spectra. We believe this to be a consequence of phospholipid, which would not appear in the aqueous extract, contributing to the phosphodiester peak in vivo.

Breast Neoplasms↗
PubMed1991

Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1.

The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer.

Aged↗
PubMed1990

Demonstration of blood flow patterns in human soft tissue sarcomas using 99mTc-labelled hexamethyl propyleneamineoxime.

Blood flow patterns have been studied in 28 patients with soft tissue sarcoma (29 tumours) using 99mTc-labelled hexamethyl propyleneamineoxime with planar views of the tumour-bearing region. Tumour:background ratios ranged from 1.13 to 6.60 (mean 2.74) and maximum:minimum tumour ratios (between peripheries and centres of tumours) ranged from 1.34 to 32.0 (mean 4.70). In eight of 29 tumours (seven of which were involving the trunk) the tumour could not be identified. This study demonstrates that the blood supply to soft tissue sarcomas is generally greater than that to adjacent normal tissues and that tumour centres are relatively underperfused compared with the tumour periphery. In this heterogeneous series there was no clear-cut relationship between blood flow and histological grade or type.

Adult↗
PubMed1990

An evaluation of 99mTc-HMPAO uptake in cerebral gliomas--a comparison with X-ray CT.

Nineteen patients with biopsy-proven cerebral gliomas were studied with 99mTc-HMPAO single photon emission tomography (SPECT) imaging and X-ray computed tomography (CT). The uptake of 99mTc-HMPAO was correlated with tumour size and morphology as shown by X-ray CT, and overall patient survival. It appears that uptake of 99mTc-HMPAO is associated with larger, ill-defined tumours and was an adverse factor in patient survival. In those tumours with normal or increased uptake, 99mTc-HMPAO imaging is useful in distinguishing the tumour margin from surrounding oedema.

Brain Neoplasms↗
PubMed1990

The effects of single dose oral hydralazine on blood flow through human lung tumours.

Hydralazine has been shown to reduce tumour blood flow and to potentiate the cytotoxicity of melphalan and bioreductive agents in mice. In order to determine whether such a strategy might have clinical potential, a study was undertaken to investigate the effects of hydralazine on blood flow through human tumours. Twenty-two patients with carcinoma of the bronchus received a single oral dose of hydralazine in the range 25 to 150 mg (0.37-2.86 mg/kg) according to age and acetylator status. Tumour blood flow was assessed by single photon emission computed tomography (SPECT) performed 10 min following intravenous 99Tcm-HMPAO on two occasions 2-8 days apart, the second being performed 60 min after hydralazine administration. In 20 evaluable patients, hydralazine caused a 38% increase in blood flow through the whole tumour (p = 0.007) and a 28% increase in flow through the tumour centre (p = 0.03) with greater increases occurring in patients sustaining greater falls in peripheral resistance. Tumour vascular resistance fell indicating active vasodilation in arterioles supplying tumours. Side-effects due to hydralazine were reported by eight patients.

Administration, Oral↗
PubMed1990

Thyroid imaging using positron emission tomography--a comparison with ultrasound imaging and conventional scintigraphy in thyrotoxicosis.

Forty-six comparative studies were performed on 41 patients with hyperthyroidism. Clinically these comprised two groups: those with Graves' disease, and those with multinodular goitre. All patients underwent an ultrasound examination and positron emission tomography (PET) using 124I, then gamma camera pinhole imaging following their 131I therapy administration. Although the 131I pinhole imaging was not performed for diagnostic purposes, there was good correlation (78% agreement) between it and 124I PET in determining relative lobe size. Hence either imaging modality could be used as an indicator of the relative radiation dose delivered to each thyroid lobe at a macroscopic level. In terms of gland morphology the PET images corresponded well to the high resolution ultrasound images (78% agreement), unlike the pinhole images which correlated poorly (only 28% agreement). The results showed that PET imaging gives better anatomical and physiological detail than 131I pinhole imaging. In 77% of cases where the pinhole image showed a uniform distribution of radioisotope, the improved spatial resolution of the PET images revealed non-homogeneous distribution indicating a non-uniform distribution of radiation dose. Since all dosimetry calculations are based on the assumption of uniform distribution of radioiodine, this non-uniformity could possibly have important consequences in the outcome of radioiodine therapy in thyrotoxicosis.

Adult↗
PubMed1990

Comparison of 5-fluorouracil pharmacokinetics following intraperitoneal and intravenous administration using in vivo 19F magnetic resonance spectroscopy.

Intrahepatic pharmacokinetic studies of 5-Fluorouracil (5 FU) metabolism following intravenous and intraperitoneal administration have been undertaken in four patients using in vivo 19F nuclear magnetic resonance spectroscopy. Following intravenous administration, 5 FU decayed with "half times" ranging from 5 to 17 min. There was considerable variation of 5 FU pharmacokinetics between patients following intraperitoneal administration. Peritoneal contamination by infused 5 FU was considered to be a significant problem in one patient. A technique for providing superficial signal suppression was therefore investigated and its efficacy for excluding signal from the peritoneal space has been demonstrated. Owing to the potential for contamination from peritoneal 5 FU, the accumulation of fluoro-beta-alanine (FBAL) is a more reliable indicator of drug catabolism than the measurement of unlocalized "hepatic" 5 FU. Rapid intrahepatic catabolism of 5 FU to FBAL was demonstrated in all patients. However, there was greater pharmacokinetic variation following intraperitoneal administration than following intravenous administration. Therapeutic implications of intravenous compared with intraperitoneal administration of 5 FU are discussed.

Fluorouracil↗
PubMed1989

Radiation dose assessments in radioiodine (131I) therapy. 1. The necessity for in vivo quantitation and dosimetry in the treatment of carcinoma of the thyroid.

In order to destroy thyroid cancer metastases by radioiodine an average tissue dose of 80-300 Gy is needed. Such high doses can be expected, following the administration of the conventional 5.5 GBq of 131I, only if both the percentage uptake per gram in the target tissue and the effective half life of the radioiodine in it are higher than well-defined threshold values, and if every dimension of the tissue exceeds several millimeters. The fulfillment of such favourable conditions in actual clinical cases can only be confirmed by in vivo quantitation of the absorbed dose achieved as a result of the administration of radioiodine.

Carcinoma↗
PubMed1989

Radiation dose assessment in radioiodine therapy. 2. Practical implementation using quantitative scanning and PET, with initial results on thyroid carcinoma.

We have designed special high-resolution, low-sensitivity collimators for a dual-headed whole-body scanner for imaging and quantifying therapy levels of iodine-131. In addition, we have used positron emission tomography (PET) with a low-cost large-area PET camera to achieve improved accuracy in the estimate to tumor mass. The physical performance of these two imaging systems is described. In order to illustrate the practical implementation of these systems for the assessment of radiation dose to normal and tumour tissue during radioiodine therapy, three clinical examples are reported, and a summary of the initial clinical results obtained from 16 patients with carcinoma of the thyroid is presented. The dose to normal thyroid remnants for patients undergoing ablation ranged from 16 to 400 Gy, while the dose to involved neck nodes ranged from 2.5 to 33 Gy for patients undergoing post-ablation radioiodine therapy. In one patient with distant metastasis in the spine, a dose of 100 Gy was achieved. The techniques described in this paper can be used to determine if sufficient activity can be accumulated in tumours to provide a therapeutic effect while minimising irradiation of normal tissues by avoiding administrations which do not provide tumouricidal radiation doses.

Carcinoma↗
PubMed1989

Technetium-99m HMPAO and SPECT in the assessment of blood flow in human lung tumours.

In order to assess the blood flow patterns through human lung tumours, 20 patients received 400-750 MBq 99TcmHMPAO intravenously 10 min before single photon emission computed tomography (SPECT). Ratios of uptake in the whole tumour relative to normal lung ranged from 0.35 to 1.53 (mean 1.01) with eight tumours showing less uptake than normal lung and ten showing greater uptake. In one patient the tumour was not distinguishable from surrounding lung and in another a large pleural effusion prevented evaluation. Tumour: lung ratios for central tumour regions ranged from 0 to 1.83 (mean 0.80) with 13 showing lower uptake than normal lung and five showing greater uptake. Duplicate scans were performed in eight patients demonstrating satisfactory reproducibility. This technique provides a simple and reproducible method for the assessment of tumour blood flow.

Adult↗