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J Bomanji

Publications and source records attributed to J Bomanji.

65 records · Page 4Linked to original sources

Characterisation of ocular melanoma with cutaneous melanoma antibodies.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.

Antibodies, Monoclonal↗

Radioimmunoscintigraphy of ocular melanoma with 99mTc labelled cutaneous melanoma antibody fragments.

The possibility of using radiolabelled monoclonal antibody fragments to image uveal melanomas has been assessed in a pilot study. 99mTc labelled F(ab')2 fragments of MoAb 225.28S raised against cutaneous melanomas were used. Initially 10 patients were imaged. In five patients the clinical findings were typical of uveal melanoma. Immunoscintigraphy was positive in all five cases. In a further five patients there was doubt about the diagnosis. One was though to have a choroidal haemangioma but failed to respond to treatment and immunoscintigraphy was positive, suggesting a diagnosis of melanoma. Two patients were assigned a diagnosis of choroidal haemangioma, one of melanocytoma or possible retinal pigment epithelium carcinoma, and one of metastasis. Immunoscintigraphy was negative in all these four cases. In combination with established diagnostic tests immunoscintigraphy may have a part to play in differentiating uveal melanoma from other similar tumours.

Adult↗

Radionuclide evaluation pre- and postextracorporeal shock wave lithotripsy for renal calculi.

Forty-two patients were evaluated pre- and postextracorporeal shock wave lithotripsy (ESWL) using [99mTc]DTPA renography. A quantitative evaluation showed that the relative renal function decreased 2-3 days post-ESWL on the treated side, and the parenchymal transit time index (PTTI) increased 2-3 days post-ESWL (p less than 0.001) on the treated side and returned to the pretreatment level by 3 wk post-ESWL. The untreated side showed an increase in PTTI 2-3 days post-ESWL (p less than 0.01), which returned to normal by 3 wk post-ESWL. A significantly greater increase in PTTI was seen in patients who received greater than 1,000 shocks as compared with those who received less than 1,000 shocks. Five patients developed obstructing uropathy post-ESWL, when stone fragments caused ureteric obstruction.

Humans↗

Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison.

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.

3-Iodobenzylguanidine↗

Imaging of carcinoid tumors with iodine-123 metaiodobenzylguanidine.

Scintigraphy with 123I-radiolabeled metaiodobenzylguanidine (MIBG) was performed successfully in two patients with metastatic carcinoid tumor. The scintigraphic findings show diversity of the tumor deposits in the uptake of [123I]MIBG in the same patient and between patients.

3-Iodobenzylguanidine↗

Quantitation of iodine-123 MIBG uptake by normal adrenal medulla in hypertensive patients.

Eighteen hypertensive patients with a clinical suspicion of pheochromocytoma and raised or borderline raised plasma catecholamine and urinary vanillyl mandelic acid (VMA) levels were studied by scintigraphy using 123I-labeled metaiodobenzylguanidine (MIBG). None of these patients had any scintigraphic evidence of pheochromocytoma at the time of study or on subsequent clinical follow-up. A quantitative approach was taken to calculate the adrenal medullary uptake of [123I]MIBG in these patients. Three different methods of quantitation were evaluated using data acquired from an anthropomorphic phantom and analysed by three independent observers. In the patient studies 34 out of 35 adrenal medullas were visualized with uptake in the range of 0.01-0.22% of the administered dose 22 hr postinjection which was calculated using the preferred quantitation method. This is an appropriate control group range for comparison with patients who have proven norepinephrine and epinephrine secreting tumors. A quantitative approach to [123I]MIBG imaging provides an important tool for studying adrenomedullary pathophysiology.

3-Iodobenzylguanidine↗

Radiolabeled octreotide. What lessons for antibody-mediated targeting?

Octreotide is a synthetic analog of the peptide hormone somatostatin (SMS). A wide variety of tumors express enhanced numbers of SMS receptors, notably neuroendocrine tumors and lymphomas, but also some of the more common adenocarcinomas. Octreotide contains only eight amino acids, some of which are in the (D) configuration in order to enhance the stability of the molecule in vivo. Tyrosine and DTPA-containing analogs of octreotide have been synthesized and labeled with iodine-123 and indium-111, respectively, with the intention of targeting SMS receptor-containing tumors for diagnostic purposes. Both radiopharmaceuticals demonstrate a high sensitivity and specificity for these tumors, indicating a clinical role for these agents in management of these diseases. Lessons can be learned from the success of these agents when designing improved antibody-based molecules. Tumor uptake of radiolabeled octreotide is very rapid, occurring within minutes of administration. Blood clearance is also rapid, such that tumors are soon visible even in areas of high blood background. An interesting finding has been the differences between the pharmacokinetics of the iodinated and indium-labeled species. Although the majority of 123I-Tyr3-octreotide undergoes hepatobiliary excretion, 111In-DTPAPhe1-octreotide is eliminated predominantly by the kidneys. These results suggest that the smallest possible antibody-like tracers are likely to have advantages over native immunoglobulins and conventional Fab-like fragments.

Adenocarcinoma↗

Acipimox does not augment thallium-201 redistribution in the fasting state.

BACKGROUND: Recently oral glucose loading and a thallium-glucose insulin infusion have been used to augment myocardial uptake of thallium-201 (TI-201). Acipimox is a nicotinic-acid derivative that reduces serum free fatty acid (FFA) levels and enhances myocardial glucose uptake. This study was performed to assess the effects of acipimox on TI-201 redistribution. METHODS: Fourteen patients with coronary artery disease underwent 2 successive TI-201 perfusion studies. Stress was performed by adenosine coupled with ergometer exercise. Patients received either 500 mg of acipimox or placebo immediately after stress, and images were acquired. Redistribution imaging was carried out after 4 hours. Patients returned after 7 to 14 days for a repeat stress protocol, receiving the alternate test article. Both studies were carried out under identical conditions with identical medication with the patient in the fasting state. Image analysis was conducted quantitatively with polar plots and by using segmental uptake as a percentage of maximal counts with a 9-segment model. RESULTS: There were no significant differences between the acipimox and placebo arms of the study of hemodynamic parameters. On polar plot analysis, there were no differences between acipimox and placebo for mean values of stress defect extent (97 +/- 16.1 vs 96.5 +/- 18.8 pixels), defect severity (532.2 +/- 120 vs 537 +/- 133.9 standard deviations [SDs]), for defect reversibility (61.7 +/- 18 vs 55.4 +/- 15.3 SDs), and percentage reversibility (21.2% +/- 5.5% vs 19.2% +/- 5.8%), respectively. Similarly, on segmental uptake analysis there was no significant difference between the acipimox and placebo arms with regard to the proportion of segments classified as normal, fixed defect, reversible defect, or reverse redistribution. CONCLUSION: Although acipimox has been shown to augment myocardial glucose uptake and myocardial glucose uptake has been shown to improve cellular uptake of TI-201, in the fasting state acipimox does not enhance the redistribution after stress. This may be because serum insulin levels are not increased by acipimox, and insulin is instrumental in enhancing the joint transport of glucose and TI-201 into myocytes.

Adenosine↗

Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery.

BACKGROUND: The use of dopamine to protect the kidneys against hypoperfusion injury remains controversial with little clinical evidence of benefit and increasing concerns regarding safety. In this double-blind, prospective, randomised study, we investigated the effect of dopamine infusion (2.5 microg/kg/min) on glomerular filtration rate (GFR) and tubular injury in patients undergoing routine cardiopulmonary bypass (CPB). METHODS: Forty eight patients were randomly assigned to receive intravenous dopamine or saline from induction of anaesthesia until 48 hours post-operatively. There were no differences in mean age, bypass time or pre-op creatinine in the 36 patients (33 men) who completed the study. 51Cr-EDTA GFR (ml/min/1.73 m2) was measured pre-operatively and on day 5 only. Urinary markers of tubular injury (albumin, N-acetyl glucosaminidase, NAG; retinol binding protein, RBP) were measured pre-operatively, and on days 1, 2 and 5. RESULTS: GFR was preserved equally in both groups. All patients demonstrated significant tubular injury but urinary levels of NAG and RBP were lower in the dopamine group (41%, p=0.057 and 41%, p=0.007, respectively) on the first post-operative day. CONCLUSION: We conclude that low dose dopamine infusion may reduce renal tubular injury following CPB in patients with normal or near normal baseline renal function.

Acute Kidney Injury↗