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 obtainedâ€”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 axillaâ€”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.

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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 Iâ€”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 Iâ€”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 sites 2 24

. Fingers. t Toes. * Number injection sites.

Six patients received normal goat gamma globulin above the diaphragm, and inguinal concentrations with labeled with 1-13 1, administered subcutaneously in a tumors below the diaphragm. This group of five patients total of 24 injection sites (Table 2); in these there was no had a total of 18 injection sites, and foci of radioactivity concentration of radioactivity in the axillary or inguinal in nine nodal groups. For the fifteen patients in the areas, except in Patients 165 and 197. In both of these control group, there were nine presumably false-positive cases, mechanical obstruction could be the basis for the findings ( 17%) from 54 injection sites. foci of radioactivity. In Patient I65 the labeled antibody was observed in the right inguinal area, where a recent orchiectomy had been performed. Similar concentration DISCUSSION of radioactivity had been observed shortly after the bi In studies of the lymphatics radionuclide-labeled lateral inguinal node dissection for carcinoma of the colloids have been used mainly for the demonstration of vulva. In the other case (No. 197) the metastases in the lymph drainage patency and the normal location of axillary nodes from the breast were massive. lymph nodes. Since these colloids are not target-oriented, In ten of the fifteen control patients who received I- and because they concentrate in lymph nodes by a fil 131-labeled antibodies to CEA, with a total of 36 in tering mechanism, the demonstration of a node indicates jection sites, no abnormal concentration of radioactivity only that the node is patent to flow, not that tumor is was observed in either the inguinal or axillary regions either absent or present. The absence of a focus of ra (Table 3). In five patients, however, the I- 13 1-labeled dioactivity in a region of expected nodal concentration antibody localized in lymph nodes. Radioactivity was may indicate that afferent lymph passages are blocked seen in the left and right axillary nodes in one patient by tumor or that there is no lymph node present. On the with cancer of the esophagus (Fig. 3), and in inguinal other hand, the demonstration of a lymph node by ra nodes of four patients with cancer of the common bile dionuclide colloids does not rule out metastatic carci duct, colon, or duodenum (Table 4). Interestingly, the noma in that node. axillary concentration of antibody occurred with a tumor One of the first demonstrations of lymph nodes with

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TABLE3. LYMPHOSCINT1GRAPHYWITh1.131ANTIBODYTO CEA(CONTROLPATIENTS-NEGATiVE RESULTS)

findingsaxillary PatiantPlasmainguinalno.ng/mlCEAInjectionLymphoscinti@aphic Primarytumor sftesnodes nodes Comments

150 100 Adenocarcinoma rectum; Dukes' C F andV Nag Nag liver metastasas (4)@

177 2.7 Adenocarcinoma rectum; Dukes' C F and Nag Nag (4)

19 1 6.5 Adenocarcinoma rectum; Dukes' C T (notdone) Nag (2)

169 4.5 Adenocarcinoma;pancreas FandT Nag Nag (4)

162 0.1 Papillaryadenocarcinoma;ovary FandT Nag Nag (4)

184 0.2 Cystadenoma ovary; FandT Nag Nag (4)

192 0 Adenocarcinoma; ovary FandT Nag Nag abdominalmetastasas (4)

167 244 Adanocarcinoma;ovary FandT Nag Nag vaginal metastases (4)

185 12.6 Adanocarcinoma;endomatrium FandT Nag Nag myometrial invasion (4)

190 396 Adanocarcinoina; prostate T (notdona) Nag (2)

Totalsites Totalpositivesites 0 36

. Fingers. t Toes. @ Numberinjectionsites.

a labeled antibody was reported by Order et al. (8) with five subjects. The palpable axillary nodes in Patients I06, 1-131-labeled antiferritin immunoglobulin. They per 110, 131, and 156 were unquestionably involved with formed lymphoscintigraphy in patients with lymphomas carcinoma clinically. and breast carcinoma. The antibody to ferritin, however, Although the production of carcinoembryonic antigen does not appear to have the degree of specificity pos in primary carcinomas of the breast is usually quite low, sessed by antibodies to tumor-associated antigens, such once the tumor has metastasized the incidence of in as CEA and AFP. creased plasma levels of CEA is remarkable. Stolbach In our study of women with breast cancer, the accu Ct al. (9) reported that twice as many patients with re racy of detecting metastases in the ipsilateral axillary current carcinoma had elevated CEA levels compared nodes was I00%. Although the axillary nodes were sur with those in remission. In a study of 742 postoperative gically examined in only two patients (Nos. 118 and patients with breast cancer, Myers et al. (10), found 125), the history and clinical findings firmly supported elevated plasma CEA levels in 14.8% of patients with the diagnosis of ipsilateral metastases in the remaining clinical stage I breast carcinoma, 23.7% with stage II,

Volume 20, Number 12 1247 DELAND, KIM, CORGAN, CASPER, PRIMUS, SPREMULLI, ESTES, AND GOLDENBERG

PATIENTS)LymphoscintigraphicPatientPlasmaTABLE 4.LYMPHOSCINT1GRAPHYWITH I-131 ANT1BODY-CEA(CONTROL

inguinalno.ng/mlPrimaryCEAInjectionfindingsaxillary tumorsitesnodes nodes 189 612 Adenocarcinomasigmoid;Dukes'cancer F andV Nag left (4)@

181 1.3 Adenocarcinomacolon;Dukes'cancer FandT Nag leftand (4) right

179 59 Adenocarcinoma;duodenum FandT Nag left and (4) right

180 4.3 Adenocarcinoma;commonbileduct FandT Nag leftand (4) right

142 12.8 Adenocarcinoma;distalesophagus F left and (notdone) (2) right

Totalsites Totalpositivesites 9 18

. Fingers. t Toes. * Number injection sites.

40.5% with stage Ill, and 73.1% with stage IV. medial half (and areolar area) of the breast as compared An interesting and possibly important finding was the with the lateral half. Accordingly, the concentration of concentration of radioactivity in the contralateral axil radionuclide-labeled antibody in the contralateral axil lary lymph nodes of four patients. In only one of these lary nodes may be a demonstration of cross-over me cases (No. 110) were the contralateral nodes palpable tastases. In Patient 110 the nodes in the contralateral (6 cm X 6 cm). The absence of palpable nodes, however, axilla were clinically metastatic, being hard and enlarged does not rule out metastases, since none were palpated (5 cm X 7 cm). In Patients 131 and 141, the lesions were in the two patients undergoing mastectomy at the time in the medial halfofthe breast, increasing the probability of this study, and both demonstrated metastases. The of contralateral metastases. The possibility of CEA possibility ofcontralateral axillary metastases must be draining to and becoming trapped in the nodes of the considered in view of the lymphatic drainage and the opposite side must also be considered. Under these location of the breast carcinoma. conditions it is reasonable to expect that the lymphatic The lymphatic drainage from the mammary tissue is channels to the contralateral side are open and actively primarily toward the axillary lymph nodes of that side. draining. Less predominant are those channels that terminate in The concentration of 1-131-labeled antibody to CEA the internal mammary nodes and the transverse cervical in the clinically malignant lymph nodes of the con nodes. Of significance is the interconnection of the tralateral axilla might be due to metastases or to se deeper lymphatic channels with those of the skin. By questered CEA antigen, through functionally patent these anastamoses, drainage from one breast may be to cross lymphatic channels. In cases of fibrosis following the opposite breast and axillary lymph nodes. Although radical mastectomy or extensive metastases, normal the ipsilateral nodes are most commonly involved in lymphatic channels are blocked, and the lymph passes breast carcinoma, metastases to the contralateral axil through collateral channels to the opposite breast or lary nodes occur particularly from carcinomas located axilla. In advanced carcinoma of the breast with massive in the medial halfofthe breast (11). The increased in axillary metastases, retrograde flow of the tumor has cidence of lymphatic drainage medially was demon been demonstrated as far distal as the ipsilateral wrist strated by Handley (12), who found that metastases to (13). After dissectionof the axilla, Bobbio et al. (14) the internal mammary chain of lymph nodes occurred demonstrated the transverse lymphatic routes to the live times as frequently with cancers located in the opposite axilla by lymphangiography. On the other hand,

I248 THE JOURNAL OF NUCLEAR MEDICINE CLINICAL SCIENCES INVESTIGATIVE NUCLEAR MEDICINE it cannot be concluded that metastases are definitely lished detection techniques such as bronchoscopy (15). present in those cases where there is no evidence of tumor These initial studies of immune lymphoscintigraphy with nictastases. The possibility of captured CEA antigen radioactive antibodies to CEA in breast cancer encour from the carcinoma must then be considered. Evidence age further investigation of this application of cancer of a similar mechanism has been demonstrated by Nossal radioimmunodetection, especially in other tumor types et al. (15,16). They showed that antigens (bacterial and with other cancer localizing antibodies. antibodies to human serum albumin complexed to HSA, and IgG) were vigorously taken up by both primary and secondary follicles. Most of the antigen trapped in fol licles were extracellular and persisted for at least 3 wk. ACKNOWLEDGMENTS The labels were found most frequently at or near the Supportedin part by National Institutesof Health Contract No. surface of fine cell processes, many of which were NCI-NOI-CB-6401 1-35, NIH Grant No. CA-17742 and a Veterans branches of dendritic follicular reticular cells. These Administration research grant. authors concluded that follicular antigens in a primary follicle can encounter natural antibody on the surface of certain antigen-reactive lymphocytes. REFERENCES By administering the labeled antibodies in lymphatic channels not associated with the lymph drainage of the I. SI1I@RMAN Al, TER-POGOSSIAN M: Lymph node concentration of radioactive colloidal gold following interstitial injection. Cancer neoplasm, a level of confidence in antibody lymphos 6:1238-1240,1953 cintigraphy is gained. For example, in ten patients with 2. HAUSLiR W, ATKINS HL, RICHARDS P: Lymph node scanning a total of 36 injection sites (Table 3) metastases to ax with 99mTcsulfur colloid. Radiology 92: 1369- I 37 1, I 969 illary or inguinal lymph nodes would be unlikely. In these 3. (jOODROINDA, FINSTONPA,COLOMBETTILG,Ctal: In for patients no concentration of radioactivity was observed imaging: Iymphnode visualization. Radiology 94: 175-178, I 970 in these nodal groups. In fiye patients with carcinomata 4. ALAvI A, STAUM MM, SHrsoL BF, et al: Technetiumâ€”99m that normally would not drain into axillary or inguinal stannous phytate as an imaging agent for lymph nodes. J Nuci lymph nodes, however, focal concentration of radioac Med 14:422-426, 1978 tivity was observed in these regions (Table 4). Although 5â€¢EGI GN: Internal mammary lymphoscintigraphy. Radiology I I 8: the number of patients is small, four with lesions below 101-107,1976 6. GAR/oN AL: Preparation of99mTc antimony sulfide colloid. ml the diaphragm demonstrated inguinal activity and the J App! Radial Isot I6: 613, I965 one with a lesion above the diaphragm showed axillary 7. GOLDENBERG DM, DELAND FH, KIM EE,etal: Use of radio activity. These findings correlate with the general divi labeled antibodies to carcinoembryonic antigen for the detection sion of lymphatic drainage in the torso. Carcinoma may andlocalizationofdiversecancersbyexternalphotoscanning.N spread to lymph nodes peripheral to the primary site of LiiglJMed298: 1384-1388,1978 8. ORDER SE, BLOOMER WD, JoNEs AG, et al: Radionuclide the tumor. In 1849 Virchow observed that by retrograde immunoglobulin lymphangiography: a case report. Cancer 35: flowcarcinoma of the uterus may metastasize to inguinal 1487-1492,1975 lymph nodes and carcinoma of the stomach or pancreas 9. STOLBACH LL, INGLIS RR, LIN CW, et al: Measurement of may spread to the lower lumbar nodes (17). Regan isoenzyme, HCG, CEA, and histaminase in the serum and The possibility of nonspecific attachment of the ra malignant effusion fluids of patients with carcinoma of the breast, ovary,lung.In Oncodet'elopmenialGeneExpression.Fisman diolabeled antibodies to receptor sites in lymph nodes WH, Sell S. eds. New York, Academic Press, 1976, pp 433- also must be considered. In six patients I- I 31-labeled 443. normal goat IgG was administered in the hands and feet, 10. MYERS RE, SUTHERLAND DJ, MEAKIN JW, et al: Carci and no concentration of radioactivity was observed in 22 noembryonic antigen in breast cancer. Cancer (suppl) 42: axillary or inguinal areas. In only two lymph-node areas 1520-1526,1978 II. ACKERMANLV, DEREGATOJA: Mammary gland. In (â€˜ancer. was concentration of radioactivity observed, and lym Diagnosis.Treatment,and Prognosis.4th Ed.,St. Louis,C. V. phatic obstruction was present in both. Mosby Co., 1970, pp 845. The intralymphatic application of radiolabeled anti /2. HANDLEYRS:Prognosisaccordingtoinvolvementofinternal bodies to a tumor-associated antigen (CEA) has dem mammary nodes. Ada Un mt Cancer 15: 1030-1031, 1959 onstrated excellent target specificity for regional met /3. HAAGENSEN CD: The spread ofcancer in the lymphatic system. In TheLymphaticsin Cancer,HaagensenCD, FeindCR, Herter astatic cancer spread. The major limitations appear to FP, Ctal. Philadelphia, W. B. Saunders Co., 1972, pp 44-45 be that it is limited to those neoplasms that contain CEA, /4. BoBislo P, PERACCHIA G, PELLEGRINO F: Connessioni linfa and technical problems with the administration of the tiche presternalifra Ic regioni mammariedci due lati. Ateneo antibodies in lymph routes not readily accessible to Parniense33 (suppl):95-101,1962 routine techniques (e.g., pulmonary carcinoma). The /5. NOSSALGJV, ABBOTA, MITCHELLJ, et al: Antigens in im former can be overcome by the use of different tumor munity, XIV. Electron microscopic radioautographic studies of antigen capture in the lymph node medulla. J Exp Med 127: associated antigens and the latter by development of 263-276,1968 lymphoscintigraphy in conjunction with other estab 16. NOSSAL GJV, ABBOT A, MITCHELL J, et al: Antigens in im

Volume 20, Number 12 I249 DELAND, KIM, CORGAN, CASPER, PRIMUS, SPREMULLI, ESTES, AND GOLDENBERG

Ifluflity, XV. Ultrastructural features of antigen capture in pri- CD, Feind CR. Herter FP, et al. Philadelphia, W. B. Saunders nury and secondary lymphoid follicles. J Exp Med I 27: 277â€”290, Co., I 972, p 51 1968 I.'@.BETIIUNE DCG, MULDER DS, CHIU RCJ: Endobronchial 17. VIRcilow R: Zur Diagnose der Krebse in Unterleibe. Die lymphoscintigraphy (EBLS). J Thoracic Cardiovasc Surg 76: mcdicinischcreform. In TheLymphaticsin Cancer,Haagensen 446@452,1978

ANNOUNCEMENTOF BERSON-YALOWAWARD

The Educationand ResearchFQundationof the Societyof Nuclear Medicineinvitesmanuscriptsfor consideration for the Fourth Annual Berson-YalowAward. Work will be judged upon originality and contribution to the fields of basicor clinical radioassay.Thewinning author will receivea monetaryawardof $750.O0andthemanuscript will be presen'ed at the 27th Annual Meeting of the Society of Nuclear Medicine in Detroit, Ml, June 24-27, 1980.

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1250 THE JOURNAL OF NUCLEAR MEDICiNE