Pretargeted immunoscintigraphy in patients with medullary thyroid carcinoma

Abstract

Summary To evaluate the use of pretargeted immunoscintigraphy (ISG) in the diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC), we studied 25 patients with histologically proven disease; ISG was repeated after surgery in two patients. The antibody, either an anticarcinoembryonic antigen (CEA) or an antichromogranin A (CgA) biotinylated monoclonal antibody (MAb) or a cocktail of the two biotinylated MAbs was first injected. After 24 h, avidin was administrated i.v., followed by "'In-labelled biotin 24 h later. Fifty-two lesions were visualised. Six primary tumours, diagnosed by increased calcitonin levels, were all correctly diagnosed; 47 recurrences, also suspected by blood tumour markers, were detected and confirmed by cytology or histology. In one case, single photon emission tomography allowed the detection of small lymph nodes with a diameter of 4 -7 mm. These lesions, not judged neoplastic by ultrasound, were confirmed to be neoplastic by fine needle aspiration. Pretargeted ISG correctly localises primary tumours and recurrences in MTC patients, when the only marker of relapse is serum elevation of calcitonin. With this three-step pretargeting method, cocktails of potentially useful MAbs can be used, avoiding false-negative studies that may occur when CEA or CgA are not expressed.Keywords: medullary thyroid carcinoma; monoclonal antibody; avidin-biotin Medullary thyroid carcinoma (MTC) arises from calcitoninsecreting parafollicular cells in the thyroid. Both the sporadic and the familial form are treated by surgery (Chong et al., 1975;Rossi et al., 1980), as the efficacy of radiotherapy is limited (Samaan et al., 1988) and chemotherapy is ineffective (Rougier et al., 1983;Brunt and Wells, 1987). Early diagnosis of recurrence or metastasis and accurate localisation of recurrent disease are very important prerequisites for successful surgical excision.Elevated serum calcitonin (Ct) is considered to be a marker for MTC. High serum levels of Ct and carcinoembryonic antigen (CEA) can often be found in patients with recurrent disease several years before it becomes clinically apparent, but, at present, no efficient and specific method is available for the localisation of recurrences.Morphological imaging techniques (ultrasonography, US; computerised tomography, CT; magnetic resonance imaging, MRI) are routinely used to confirm and localise a biologically detected recurrence but are not always adequate because of topographic polymorphism and the small size of tumour recurrences at an early stage of development (Schwerk et al., 1985;Frank et al., 1987;Crow et al., 1989).Several methods based on tumour avidity of non-specific radiopharmaceuticals such as [99"Tc](V)DMSA, '3I11231-MIBG and 20'T1 have also been designed for this purpose, with variable results (Arnstein et al., 1986;Hilditch et al., 1986;Baulieu et al., 1987;Clarke et al., 1987;Hilditch, 1987; Clarke et al., 1988;Hoefnagel et al., 1988;Guerra et al., 1989;Adams et al., 1990;Charkes et al., 1990;Udelsman et al., 1993).In the attem...

Chromogranin A: its clinical value as marker of neuroendocrine tumours

“…This has been proven for CgB in the PC12 neuroendocrine cell line [43]. This provides the opportunity to develop an in vivo imaging technique, using immunoscintigraphy with monoclonal antibodies against CgA or CgB [93][94][95][96]. Such a 'chromogranin scan' might have the obvious advantage to be specific for neuroendocrine tissues, in contrast with the widely used somatostatin receptor scintigraphy (Octreoscan, Mallinckrodt), which also visualizes lymphatic tissues, such as inflammatory infiltrates and lymphomas [97].…”

“…Such a 'chromogranin scan' might have the obvious advantage to be specific for neuroendocrine tissues, in contrast with the widely used somatostatin receptor scintigraphy (Octreoscan, Mallinckrodt), which also visualizes lymphatic tissues, such as inflammatory infiltrates and lymphomas [97]. Preliminary data have been presented by Magnani et al [93,96], Colombo et al [94] and Siccardi et al [95] about the use of a three-step pretargeted immunoscintigraphy using anti-chromogranin A monoclonal antibody in patients with several neuroendocrine tumours showing a higher diagnostic accuracy than conventional imaging techniques. These data should be confirmed and be compared with a control group of patients with non-neuroendocrine neoplasms.…”

Genetic Engineering, Expression, and Activity of a Chimeric Monoclonal Antibody−Avidin Fusion Protein for Receptor-Mediated Delivery of Biotinylated Drugs in Humans

“…However, avidin has been administered to humans in 5-10 mg doses intravenously without immunologic reactions (8,16,17). The human hypo-responsiveness to avidin may arise from oral antigen feeding (18).…”

HPMA copolymer-modified avidin: Immune response

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