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Antigenin Breastcancer CLINICAL SCIENCES INVEST1GA11VE NUCLEAR MEDICINE Axillary Lymphoscintigraphy by Radioimmunodetection of Carcinoembryonic Antigenin BreastCancer Frank H. DeLand,E. EdmundKim, Robert L. Corgan, Scott Casper, F. James Primus, Ellen Spremulli, Norman Estes, and DavidM.Goldenberg Universityof KentuckyCollegeof Medicine,VeteransAdministrationMedicalCenter,andEphraimMcDowell CommunityCancerNetwork,Inc.,Lexington,Kentucky In seven women with carcinoma of the breast 1-131-labeled antIbodies to card noembryonic antigen (CEA) were administered subcutaneously in the finger webs. Subsequent scintlgraphic images demonstrated localization of radioactivity in the ipsilateral axlllary metastases of all patients and in the contralateral axillae of three. Fifteen patients wfth either gastrointestinal or genitourinary cancers were studied as controls; in 12 both the hands and feet were injected wfth antibodies to CEA and in the other three either the hands or feet. Radioactivity was observed in theinquinalnodesoffourcontrolpatientswithtumorsbelowthediaphragmandin the axillary nodes of one patient with a tumor above the diaphragm. The concen tration of antibody in lymph node metastases from breast carcinoma was 100% specific. In those lymph nodes that presumably contained no metastatic tumor but demonstrated localization of labeled antibody, retention of CEA in the nodes from tumor drainage is postulated as the receptor site for the antibody. J NucI Med 20 1243-1250, 1979 More than 25 years ago Sherman et al. (I ) demon specific deposition in lymph nodes. We now report the strated regional lymph nodes by external scintillation USC of a radionuclide-labeled antibody to a tumor-asso imaging following the interstitial administration of ciatcd antigen, carcinoembryonic antigen (CEA), for the colloidal radioactive gold. Subsequently, other labeled scintigraphic detection of axillary lymph-node metas colloids have been used for lymphoscintigraphy. Hauser tases from breast cancers. ci al. (2) reported their experience with lymph-node scanning with Tc-99m-labeled sulfur colloid. In-I 11- MATERIALS AND METHODS labeled colloids have been proposed because of certain physical advantages, such as the longer half-life of In The preparation of the I-I 31-labeled antibody to CEA I I I compared with Tc-99m (3). Alavi et al. (4) evalu antigen has been described in detail (7). After extraction ated Tc-99m-labeled stannous phytate for lymphoscin and purification of the CEA derived from a colonic tigraphy, whereas Ege (5) has shown that Tc-99m an cancer metastasis, goat hyperimmune antiserum to the timony sulfide colloid (6) may have characteristics su CEA was produced. The goat antibody to CEA was perior to those of other radiocolloids. None of these purified by absorption with human erythrocytes and colloids, however, has target specificity, but instead re passage over an immunoabsorbent of normal human fleets the patency of the lymphatic channels and non lung and spleen extracts conjugated to Sepharose 4B. Final purification was obtained by affinity chromatog ReceivedMay 2, 1979;revisionacceptedJune2, 1979. raphy with CEA antigen immunoabsorbent. The anti For reprintscontact:Frank H. DeLand,Dept.of RadiationMcdi body to CEA was labeled with I- I 3 1 by the chlora cine, Rm. N-i, Univ. of Kentucky College of Medicine, Lexington, mine-T method, and a specific activity of 5-10 .tCi/zg of KY 40536. IgG protein was obtained—slightly less than one atom Volume 20, Number 12 1243 DELAND, KIM, CORGAN,CASPER,PRIMUS,SPREMULLI,ESTES.AND GOLDENBERG of I- 13 1 per molecule of IgG. After radionuclide label patients were skin-tested for allergic reaction to goat ing, approximately 70% of the immunoreactivity with lgG, and they alsoreceivedLugol's iodine to minimize CEA remained. By means ofSephadex G-200 chroma 1-131 concentration by the thyroid gland. From 0.7 to tography, 90-95% of the labeled antibody was found to I.5 mCi of labeled antibody were administered to each elute with the IgG fraction. The labeled antibodies were patient in divided doses, depending on the number of then tested for sterility, pyrogenicity, and toxicity. injection sites. Immediately following the subcutaneous Seven women with proven carcinoma of the breast injection, the areas were massaged for several minutes, were entered into the study for determination of axillary and the patientswere requestedto exercisetheir fingers lymph-node metastases. All received I- 13 1-labeled and/or toes. By means of a gamma camera, images were antibody to CEA, which was administered subcuta routinely obtained at 24 hr and again at 48 hr if logisti neously in the webs between the fingers. cally possible. Data were stored in a laboratory computer For control studies, 21 patients with carcinomas of the and the images generated on a color display system. In gastrointestinal or genitourinary systems were selected some patients, 0.5 mCi of sodium [99mTclpertechnetate because the extremities' lymphatic channels and nodes and 0.5 mCi ofTc-99m-labeled human serum albumin would not normally be in the drainage pathways of these were administered intravenously about 1/2 hr before neoplasms. Fifteen of these patients received antibodies imaging. The technetium compounds were used to sim to CEA, while six received I-i 3 1-labeled normal goat ulate a nontarget background for the 1-13 I-labeled IgG. Both hands and feet were injected in the majority antibody to CEA, and the background was subtracted of the control patients. by computer processing (7). Metastatic carcinoma then Before administration of the labeled antibodies, the appeared as discrete foci of increased radioactivity. The WIThBREASTCARCINOMAPlasmaPatientTABLE 1. AXILLARY LYMPHOSCINT1GRAPHYIN PATiENTS Palpaple imagesComments24 no.CEAng/mIAge(yr) Primarytumor lymphnodesCEA-AB hr 48 hr 106 700 72 Scirrhous Rightaxilla mul + Rightaxilla + Rightaxilla Biopsy:infiltrating carcinoma;right tiple enlarged carcinomabreastand breast skin;boneandliver metastases 110 12.2 52 Scirrhous Rightandleft + Rightand + Leftaxilla 7yrafterleftradical carcinoma; left axilla—6cm X 6 left axillae mastectomy;boneand breast cm liver metastases 118 30 82 Adenocarcinoma;None + Leftaxilla Notdone left radicalmastectomy;1 left breast of 25 lymphnodes posftive for metastases 125 2.0 67 Ductalcarcinoma;None + Rightand + Rightand innerlowerquandrant left breast left axillae left axillae tumor-left modified mastectomy; 14of 24 lymphnodespositivefor metastases 131 3.4 50 Ductalcarcinoma; Rightaxilla2 cm + Rightand Notdone massive,fixed,inoperable right breast X 2 cm left axillae carcinoma;biopsyonly 141 7.5 61 LObularcarcinoma;Rightaxilla4 cm + Rightaxilla + Rightaxilla fixedmedialbreastmass; right breast X 4 cm biopsy only 156 4770 65 Scirrhous Leftaxilla2cm + Rightaxilla + Rightand 3yraftermodified carcinoma;left X 5 cm left axilla left axillae mastectomy; bone and breast liver metastases . 1-131 label of antibody. 1244 THE JOURNAL OF NUCLEAR MEDICINE CLINICAL SCIENCES INVESTIGATIVE NUCLEAR MEDICINE results were compared with the surgical histopathology linding where possible, or with the results of other di I agnostic procedures. RESULTS Sites of primary tumors, presence or absence of din RS ically palpable lymph nodes, and imaging results are tabulated in Table 1 for the seven patients with carci @; noma of the breast. The 1-13 1-labeled antibody to CEA concentrated in the ipsilateral axillary region in all seven, @c% although nodes were clinically palpable in only five (Fig. RIX I ). Bilateral focal activity in the axillae was observed in four patients: (a) two (Cases 110 and I 56) who had had @tIllastectomy previously and currently had systemic metastases (Fig. 2); (b) one with a massive tumor that involved the entire breast (Case I 3 1) but with palpable lymph nodes on the ipsilateral side only; and (c) one with FIG.1. Posteriorviewofrightchestandshoulderincarcinomaof nopalpablelymphnodesbutwiththeprimarytumorright breast(Patient141).Imageobtained24 hr after administration located in the medial half of the breast. We were unable of 1-131CEA-AB.Twodiscretecontiguousfoci of increasedra to obtain biopsy confirmation of the contralateral axil dioactivityin rightaxilla (arrow).RS rightshoulder;RL right lung lary lymph nodes in these patients. (radioactivitypartiallyremovedbydataprocessing). To I—To -@ 11 FIG.2. Anteriorviewofchestincarcino ma ofleftbreast.Bilateralfociofincreased radioactivity in axillae, greater on left (ax rows). ImagesobtainedTc-99monly. I- Tc-subtraction image, Tc from I; T thy roid (removed in lower small images by data proc'essing)@L = liver. I To I—To # ./ @ #1i@..@# FIG.3. Anteriorviewofchestincarcino maof esophagus(Patient142).Bilateral foci increased radioactivity in axillae (ax rows).Imagesobtainedat24hr.H heal L liver. Volume 20, Number 12 I 245 DELAND, KIM, CORGAN, CASPER, PRIMUS, SPREMULLI, ESTES, AND GOLDENBERG PATIENTS)LymphoscintI@'aphyPlasmafindingsPatientCEAInjectionaxillaryTABLE 2. LYMPHOSCINTIGRAPHYWITh 1-131 NORMAL lgG (CONTROL inguinalno.ng/mlPrimary tumorsftesnodes nodesComments 166 2.3 Papillaryadenocarcinoma;ovary F and Nag Nag Tt (4)@ 186 21.7 Mucinousadenocarcinoma;ovary FandT Nag Nag (4) 164 10.5 Papillary adenocarcinoma; F and T Nag Nag oviduct (4) 196 1.4 Squamouscell carcinoma;cervix FandT Nag Nag (4) 165 1.8 Embryonalcell carcinoma; right FandI Nag right metastasesto lungafterright testis (4) orchiectomy 197 0.7 Adenocarcinoma; left breast F and T left Nag massive metastases, left axilla and (4) lung,afterleft mastectomy Total Total positive sites
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