Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelling of white blood cells, routinely used for the detection of infection, results in the incorporation of radioactivity by polymorphonuclear leucocytes and also lymphocytes and can induce cell lesions in the latter case. The aim of this study was therefore to acquire data on the morphological and functional status of labelled lymphocytes present in the 99mTc-HMPAO leucocyte mixture and to determine the cellular consequences of labelling. The mean radioactivity associated with lymphocytes was 325 +/- 10.8 kBq/10(6) lymphocytes under standard labelling conditions. Microautoradiographic studies showed that labelling was heterogeneous (4% intensely labelled cells), which prevented calculation of the mean absorbed dose. The frequency of chromosomal aberrations (dicentrics and rings) in the labelled lymphocytes for 380 kBq/10(6) cells was 1.08 +/- 0.09 but no abnormality was observed in the unlabelled control lymphocytes. The plating efficiency of labelled lymphocytes was reduced, as compared with that for control cells, but some lymphocytes were still able to form clones and were still "alive" by radiobiological definition. It is therefore suggested that lymphocytes should be removed from 99mTc-HMPAO cell preparations before administration to patients.
Purpose: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases. Experimental Design: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use. Results: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected byAES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P < 0.01). In addition 12 extranodal metastases were found in this study of which eight were detected byAES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone. Conclusions: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.Five-year survival rate is about 60% to 80% in patients with tumor-node-metastasis stage II (no lymph node involvement) colorectal cancer and 30% to 60% in patients with tumor-nodemetastasis stage III (node-positive) disease (1 -4). Adjuvant chemotherapy improves the 5-year survival of stage III patients (5 -8) but is not commonly used in stage II patients because of its side effects (3, 4, 9). However, some patients with stage II disease may be underscored and would benefit from this treatment if a more precise staging could be obtained. Routine pathology with node detection by palpation, followed by serial macroscopic sectioning of the mesocolon, may understage the disease (10 -16). Indeed, studies using a fat clearance technique showed that most lymph node metastases involved nodes smaller than 5 mm that usually escape routine pathologic examination (10,12,17,18). Fat dissolution of surgical specimens thus improves the detection of small node metastases and thereby lessens the risk of understaging (17), but this technique is not easy to implement (18 -20).Radioimmunoguided surgery was proposed (21) to improve colorectal cancer staging, using a labeled anti -carcinoembryonic antigen (CEA) antibody Fab'-fragment (CEA-Scan). Ex vivo gamma-probe scanning of surgical specimens obta...
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