Of course, several issues still remain to be solved, including a high negative predictive value of the immunolymphoscintigraphy
Of course, several issues still remain to be solved, including a high negative predictive value of the immunolymphoscintigraphy. node metastases is usually of major importance. The sentinel node (SN) technique is now widely accepted as a minimally invasive and accurate method for identifying breast malignancy and melanoma patients with subclinical regional lymph node metastases likely to benefit from complete regional lymph node dissection (CLND) and possibly adjuvant therapy. The technique saves approximately 60% of breast cancer patients [1] and 80% of melanoma patients [2,3] without regional metastases from the risk of complications related to CLND. The SN is usually defined as any lymph node receiving direct lymph from the primary tumour site, and it is thought to be the entrance for further regional spread of the cancer, followed by delayed progression of metastases to other lymph nodes in the region [4]. The use of lymphoscintigraphy and subsequent intraoperative probe detection and use of blue dye for visual SN identification have improved patient management, morbidity, and probably also mortality. An important limitation of SN detection is the lack of knowledge before the operation as to whether the SN contains malignant cells or not. The retention in the regional lymph nodes of colloids used for SN lymphoscintigraphy only identifies the SN but is not related to the presence of malignant cells in the SNs. Excision of an SN, therefore, has to be combined with histology and immunohistochemistry to identify possible malignant cells. If malignant tissue in the regional lymph nodes could be detected preoperatively and noninvasively, permitting better selection of patients for CLND, the SN technique would be clinically greatly improved. This could lead to omission of regional lymph node surgery in node-negative patients and diminishing the extent of surgery with better preoperative planning of a one-stage procedure in node-positive patients. Immunolymphoscintigraphy might represent such a tool. Immunolymphoscintigraphy refers to scintigraphy with interstitial (subcutaneous, intracutaneous, or intratumoral) injection of a tumour-specific radiolabelled antibody for malignant lymph node imaging. A variety of radiolabelled antibodies against tumour-associated antigens have previously been studied, both in animals and humans, to test their ability to selectively target malignancy cells in lymph nodes. In the immunoscintigraphy literature, more interest has been paid to intravenous administration of radiolabelled antibodies, often with disappointing results [5,6], though a few promising studies have been reported [7,8]. By intravenous administration of the DL-Dopa radiolabelled antibody, only a small fraction of the antibody gets direct access to the target, partly due to the distribution of the antibody in the total blood volume, and partly due to a generally high and rapid hepatic uptake of foreign proteins. Therefore, a lymphoscintigraphy approach with interstitial injection of the antibody appears promising in several diseases for detection of metastatic regional lymph nodes [9,10]. Results reported have been promising, but not yet sufficiently efficient for clinical use [1113]. Will the antibody injected like a sentinel node radiopharmaceutical pass to the regional lymph nodes, but only stay there for a limited time interval permitting binding to the specific antigen if present on the DL-Dopa surface DL-Dopa of tumour cells? The aim of the study was to develop a method and obtain proof-of-principle for immunolymphoscintigraphy for identification of metastatic sentinel nodes. To do so we (1) in vitro tested and selected one of four tumour specific antibodies against membrane bound antigens expressed by human breast malignancy, (2) investigated the in vivo antigen-antibody binding in a xenograft mice model with human breast cancer, known to express the antigen and with tumours sized-like human lymph nodes, and (3) investigated if radioactively labelled antibodies were transported to and through regional lymph nodes when injected subcutaneously in healthy rabbits. A strategy to set up dual isotope immunolymphoscintigraphy for noninvasive, preoperative, malignant sentinel node diagnosis is usually finally suggested. == 2. Materials and Methods == == 2.1. In Vitro Test of Antibodies on Tissue and Cell Lines == We tested 4 different murine monoclonal antibodies known to be expressed CDC7L1 in human breast malignancy; 3 against polymorphous epithelial mucin (MUC1), an DL-Dopa epithelial transmembrane glycoprotein (clone E29 (Dako, Glostrup, Denmark), clone GP 1.4 (AbCam, Cambridge, UK), and clone 115D8 (Monosan, Uden, The Netherlands)), and one against epithelial cellular adhesion molecule.