Radiocolloid Lymphoscintigraphy in Neoplastic Disease1

[CANCER RESEARCH 40, 3065-3071. August 1980] 0008-5472/80/0040-0000$02.00 Radiocolloid Lymphoscintigraphy in Neoplastic Disease1

GuneÃ§N. Ege

Department of Nuclear Medicine. The Princess Margaret Hospital, Toronto, Ontario M4X 7K9, Canada

Abstract to the drainage lymph nodes, where the radiocolloid is lodged and a scintillation camera image providing functional, as well The transport and intralymphatic deposition of interstitially as anatomic and morphological data, is obtained (27). Because injected radiocolloid of suitable physical properties are medi lymphatic cannulation is not required, the technique is versatile ated through physiological processes and provide the means and is applicable to many more anatomic sites than is the for obtaining scintigraphic images of drainage lymph nodes lymphogram. relevant to the injection site. In a large series of patients with To date, interstitial lymphoscintigraphy has been most widely breast carcinoma, high correlation has been shown between used to study the internal mammary lymphatics in patients with the internal mammary lymphoscintigram and clinicopathologi- breast carcinoma with the objective of improving current stag cal stage of disease and prognosis. Since radiocolloid transport ing criteria (1, 7, 8, 9). The technique has also provided precise to, transit through, and deposition within the lymph node are lymph node localization for accurate parasternal radiation (4, effected through cellular elements concerned with immunolog- 6). More recently, interstitial radiocolloid lymphoscintigraphy ical mechanisms, it is proposed that the radiocolloid lympho has been utilized for visualizing pelvic lymphatics (10). scintigram be viewed not only as a technique for documenting morphologically established neoplasms in regional lymph Materials and Methods nodes but also as a modality for the recognition of functional changes which may influence the development of such neo Of the many agents used in radionuclide lymphoscintigraphy, plasms. 99mTc ASC2 (Union Carbide Corp., Tuxedo, N.Y., and Byk- Mallinckrodt CIL B.V., Retten, The Netherlands) has the most Introduction suitable properties (small uniform particle size of 4 to 12 nm) for interstitial lymphoscintigraphy (13). The use of a preformed In view of the role played by lymphatics in constituting a radiocolloid is recommended in view of the unpredictable be natural pathway for the dissemination of tumor emboli and the havior of in vivo colloids when injected interstitially (12, 19). propagation of a neoplasm remote from its origin, an accurate Experiments with rabbits have demonstrated that the primary assessment of lymphatic drainage sites from a primary tumor transport mechanism following the interstitial injection of ra is mandatory and implicit within the UICC (30) tumor-node- diocolloid is phagocytosis by tissue macrophages, although metastasis classification of tumors. Upon this appraisal rests lymphatic transport of free particles is also likely (26). In our the prediction of prognosis and a management decision appro own laboratory, studies with rabbits have shown that radioac priate to the stage of disease. Also considered, but poorly tivity in lymph nodes reaches a plateau at 2 to 3 hr (Chart 1), understood, is the function of regional lymph nodes in initiating and images or studies delayed beyond 6 hr do not contribute immunological recognition, in retarding tumor growth locally, further diagnostic or kinetic information. or in sustaining generalized tumor immunity. Saturation of lymph node sinusoids and reticuloendothelial Diagnostic modalities for providing an accurate assessment cells may occur with successive injections, showing progres of all lymphatics are limited. Palpation of superficial sites has sively diminishing uptake of radiocolloid (Chart 2). Clearance proven inadequate in determining the status of lymph nodes, of colloid from the lymph node requires 5 to 7 days, which must and criteria considered indicative of the presence or absence be remembered if a study is to be repeated. of tumor involvement have been misleading (31). The radiocolloid internal mammary lymphoscintigram is car The lymphogram utilizes contrast medium passively intro ried out following the alternating subcostal injection of 500 Â¡iC\ duced into lymphatic vessels to display normal or disrupted of "Tc ASC into the posterior rectus sheath. In patients with lymph node architecture. The necessity of cannulating lym breast carcinoma, the side corresponding to the site of primary phatics limits applicability to lymph node groups which drain a disease is injected initially in order to demonstrate any evidence suitable peripheral site with accessible lymphatic vessels. of lymphatic cross-drainage which may put the opposite par- Since tissue density differentials between normal and abnor asternal lymphatics at risk. The initial image is obtained at 3 hr, mal lymphatics or abnormal lymphatics and surrounding struc the contralateral subcostal injection is carried out, and the final tures are not great enough to accentuate the distinction, the image is obtained at 6 hr (8). A lateral lymphoscintigram is also use of computer-assisted tomography in this regard has been carried out to determine the depth of parasternal nodes (Chart confined to distinguishing enlargement and distortion rather 3/0. than intrinsic abnormality (23). A scintillation camera interface with a remote POP 11 /40 The principle underlying the radiocolloid lymphoscintigram computer uses a program for edge detection to provide full- consists of physiological transport of a radiocolloid of suitable scale isocontours of the lymphoscintigram to localize individual physical properties from an appropriate interstitial injection site lymph nodes and to determine the percentage of injected radioactivity in each node (4) (Chart 3ÃŸ). ' Presented at the UICC Workshop on Radioimmunodetection of Cancer. July 19 to 21. 1979, Lexington, Ky. 2 The abbreviation used is: 99mTcASC, "Tc-antimony Sulfide colloid.

AUGUST 1980 3065

With studies to date on reproducibility of the technique, Results anatomic validity as well as variability in normal lymphatics and drainage pathways have been documented, and criteria for Between November 1972 and October 1979, 5901 internal interpretation of the lymphoscintigram have been developed mammary lymphoscintigrams were carried out on 4669 pa and defined (1, 7, 8) (Chart 4). Radiocolloid localization within tients with malignant disease referred to The Princess Margaret any lymph node group depends upon patency of lymphatic Hospital. Variability in the position of the parasternal lymphatics pathways, the effective transport to, transit through, and dep and disparity between internal mammary nodes and standard osition within a sequence of lymphatics. Pathological or phys ized parasternal radiation fields have been demonstrated in iological processes which interfere with or modify any one of many instances (7). these mechanisms may be recognized in a deviation from the Correlation of the lymphoscintigram with histological findings normal image displayed on the lymphoscintigram (Chart 5). (22), clinicopathological stage of disease, axillary histology (8), prognosis in patients with breast carcinoma (9), and the place of internal mammary lymphoscintigraphy in the management of malignant ascites (3) has been reported. There is progressive rise in the incidence of abnormal lym phoscintigrams with advancing stages of disease in breast carcinoma (Table 1). The identification of parasternal mÃ©tas tases with lymphoscintigram, in addition to histologically veri fied axillary involvement, indicates a poor prognosis, corrobo rated by data obtained from surgical studies (8, 9, 21) (Table 2). The technique has been useful in the follow-up of patients for evaluating the extent of disease, as well as response to treatment (11).

Discussion

Chart 1. Popliteal lymph node radiocolloid uptake and total body activity Mechanical factors which impair the flow of radiocolloid from following the dorsal pedal s.c. injection of 250 Â¿iCiof"Te ASC in 3 rabbits. the injection site (hereditary lymphedema) (17), or preclude the

Chart 2. A. patient undergoing repeated internal mammary lym phoscintigraphy with 99mTc ASC demonstrates enhanced lymphatic radiocolloid uptake in the first study with diminished uptake in the second study and no visible lymphatics in the third study. Hepatic 2A radioactivity does not diminish, indicating transport of radiocolloid from the injection site through the parasternal lymphatics to the jugulosubclavian junction and venous circulation. A "Co marker denotes the sternal notch. B, the same observation in the experimental rabbit model with interstitial injection of "Te ASC on 3 consecutive Â£ Absorption from . days. Although total body radiocolloid uptake is unaffected, there is P injection site significant decrease in the popliteal node radiocolloid uptake on the second and third days. J Popliteal node B uptake

o 25.7.77 a 26.7.77 A 27.7.77

4 6 IO 2B Hours

3066 CANCER RESEARCH VOL. 40

Chart 3. In A. 3 hr following the left subcostal injection of 99mTc ASC in a patient with left breast carcinoma, parasternal lymphatics, upper left parasternal, substernal, right upper parasternal. and right 3A supraclavicular nodes are visualized. Three hr following the subse quent right subcostal injection, proximal right parasternal nodes are visualized. Lateral scintigrams with markers on the sternal notch and 21370 am 20 June 1979 21370 pm 20 June 1979 sternomanubrial junction are also obtained. Asymmetry between the 5 cm right and left parasternal lymphatics is within normal limits. Substernal +SN communication between these lymphatics would have been obscured had bilateral subcostal injections been carried out simultaneously in the first instance, ÃŸ.computerized isocontours of the lymphoscinti- VN /\030* gram indicating the percentage of injected radioactivity in individual V) "ONJ CT nodes. The full-scale size of the isocontours facilitates radiation treatment planning. XP. xiphoid process, SN. sternal notch. O QÂ°-"% cr

$ c>0.06*. "A

deposition within and transit through the node, due to neoplas- those regional to an injected antigen, keyhole limpet hemocy- tic proliferation and disruption of lymphatic pathways and anin, when infused with Microfil and examined using stereo- lymph nodal structure, have been well documented (28, 29). microscopy and radiography, demonstrated increased filling Manifestations of distal obstruction to lymphatic flow with ret with alteration of lymphatic spaces and saccule formation ad rograde tissue permeation of radiocolloid (8) have been var jacent to follicles both in the cortex and medulla. They con iously described as a "flare" (18) or "blush" (11) proximal to cluded that such multiplication and enlargement of lymphatic the site of the obstruction. Also recognized is the transient spaces with diversion of flow throughout the entire sinusoidal reversible impairment of radiocolloid deposition within the in system is an integral part of the immune reaction, serving the ternal mammary nodes of patients with breast carcinoma in the purpose of distributing antigen-containing lymph more uni immediate postoperative period, due to probable blockage of formly throughout the node, maintaining contact with receptors lymphatic sinusoids by surgical "debris" (8). of adjacent cells. Less well understood are the potential immunological impli Histologically, the lymphoreticular response occurring in cations of alterations in radiocolloid transport and deposition. nodes regional to a neoplasm is recognized in sinus macro Any colloid, although nontoxic and nonallergenic, by nature of phage proliferation, proliferation of cells in germinal centers, its foreign particulate character is a phagocytic stimulant and and migration of cells from postcapillary venules (14). a challenge to the host defense mechanisms for its appropriate These 2 observations constitute the visually apparent seque disposal. The manner in which radiocolloids are handled by lae of an immunological event and may be components of the lymphatics, which are major components of the immunological same phenomenon. It is feasible that variations in radiocolloid organ complex, may reflect an enhanced or depressed host distribution and uptake in individual nodes or node groups may immune status. reflect changes accompanying a lymphoreticular response to Davidson and Hobbs (5) in 1974 described lymphatic micro- antigenic stimuli and development of the lymphatic microcir circulatory spaces which appear in lymph nodes during an culation earlier described. immune response. In comparison with normal lymph glands, The lymphoscintigram which demonstrates relatively in-

AUGUST 1980 3067

N.M. 20159

Chart 4. Normal variation in lymph node size, distribution, lym phatic drainage, and intensity of radiocolloid uptake. A. xiphisternal cross-drainage with visualization of both parasternal chains after unilateral right subcostal radiocolloid injection. Radiocolloid uptake is accentuated bilaterally after the subsequent left subcostal injection. In 6, in a patient with pectus excavatum. left axillary nodes as well as a complete chain of right parasternal nodes extending from the diaphragm to the supraclavicular fossa are demonstrated following the right subcostal injection. Left diaphragmatic and upper paraster nal nodes appear following the left subcostal injection. In C, following the left subcostal injection, a chain of left parasternal nodes are clearly delineated. Note the lymphatic drainage pathway from the left subcostal injection site across the right thorax, to the right axillary nodes. The right parasternal nodes are visualized subsequent to the right subcostal injection.

3 hours hours

creased radiocolloid uptake (Chart 6) may therefore be inter The postulated mechanism was probable obstruction to ra preted as indicating a local lymphoreticular response to tumor diocolloid outflow from the node due to tumor emboli. Alterna antigen, the sinus histocytosis recognized in regional lymph tively, one could view this phenomenon as representing retic- nodes, which may have prognostic significance (15). Such a uloendothelial hyperplasia in response to antigenic stimulus response may be part of a sequence of events starting with the from the primary neoplasm. initial Â¡mmunohistological reaction to the presence of a neo- Boak and Agwunobi (2) report studies in inbred C3H mice plastic process in the region, concluding either with tumor bearing a syngeneic mammary carcinoma challenge, as well rejection or tumor proliferation, and replacement of the lymph as control animals bearing irradiated tumor, irradiated synge node with decreasing lymphatic radiocolloid uptake. neic spleen cells, and Dulbecco s solution in the right hind foot With histological examination of parasternal nodes removed that were given injections of 99mTc ASC in both hind feet 5 in 106 patients with breast carcinoma who had undergone weeks later. The mice were sacrificed 15 to 90 min after preoperative internal mammary lymphoscintigraphy with 198Au injection, when right and left popliteal nodes were removed, colloid, Matsuo (22) demonstrated a high correlation between weighed, and counted; results were expressed as cpm/mg. lymphoscintigraphy and pathological results. In one instance, They show inhibition of radiocolloid uptake in the right popliteal a minimal tumor deposit was demonstrated in a node which or primary node draining the tumor-bearing area relative to the had shown increased radiocolloid uptake on lymphoscintigram. left, but not in the sacral or secondary node, concluding that

3068 CANCER RESEARCH VOL. 40

Chart 5. Interpretation of the internal mammary lymphoscintigram. A. normal lymphoscintigram demonstrating discrete lymphatic aggre gates with good bilateral radiocolloid uptake. B, diminished radiocolloid uptake in the upper left parasternal nodes, compared with the lower leti and contralateral right parasternal nodes. The appearances are suspicious of abnormality. In C. although diaphragmatic and 5A xiphisternal nodes are well delineated indicating a technically satis factory injection, the left parasternal lymphatics have been disrupted with ill-defined aggregates of radiocolloid along the parasternal bor der and substernally. Note the blush of activity suggesting obstruction to lymphatic flow and retrograde tissue permeation of radiocolloid. This is an abnormal study. D. an abnormal study demonstrating complete obliteration of the distal right parasternal nodes, with vis ualization of proximal right parasternal nodes. The left parasternal nodes are normal.

N.M. 20445 N.M. 20471

6 hours 5C 5D

depressed radiocolloid uptake by regional nodes draining a macrophage function and neoplasia (20), the unequivocal elu tumor is due to a local inhibition of phagocytic activity of cidation of the mechanisms involved using interstitially injected regional lymph node macrophages. Their data show signifi radiocolloid remains to be documented. cantly depressed radiocolloid uptake in the primary drainage The possibility that the behavior of different radiopharmaceu- node in control animals as well, and their conclusion regarding ticals may distinguish lymph nodes with or without neoplastic inhibition of macrophage phagocytic function may not be infiltration is suggested by Osborne ef al. (24). In studies unique to a tumor-bearing site but does represent a nonspecific comparing 99mTcASC and "Tc-stannous phytate in rats bear process. Scintigraphic studies carried out by the same authors ing histologically confirmed lymph node mÃ©tastases from the in rabbits bearing VX2 carcinoma in the right forefoot showed transplantable Rd/3 tumor, there is a greater difference be depressed uptake by right axillary nodes of 99mTcASC injected tween normal and abnormal nodes in the uptake of "Tc- into both forefoot pads 5 weeks later. Since these animals stannous phytate than in that of 99mTcASC. Our data (12) and showed reportedly obvious tumor in the axillary nodes by 10 those of Kaplan ef al. (19) suggest that "Tc-stannous phytate, weeks, it is likely that the depressed radiocolloid uptake doc an in vivo colloid, may be a less efficacious lymphoscintigraphic umented by scintigraphy at 5 weeks was due to lymphatic agent than "Tc ASC, and the results reported reflect inade tumor invasion, rather than inhibition of macrophage phago quate lymphatic distribution rather than suppressed lymph cytic activity. node uptake specific to neoplasms. Although there is much evidence associating depressed The same authors report the use of interstitially introduced

AUGUST 1980 3069

N.M. 20447 NM20447 pm 19Februory1979 5 cm /\0.0

Chart 6. Lymphoscintigram in a patient with right breast carci OM%/\ noma. In A, right parasternal nodes demonstrate uniformly increased radiocolloid uptake compared with the contralateral lymphatics. 0, computerized calculation of the percentage of uptake of total injected radioactivity in individual lymphatic aggregates. SN. sternal notch; XP, xiphoid process

â€¢tXP /*O.IJ*

6B hours radionuclide-labeled liposomes for lymph node visualization tially may not correspond in all instances to sites of histologi- (25), postulating that, apart from imaging lymph nodes and cally verifiable neoplasm but may precede these developments detecting tumors, there may also be the possibility that such by a variable interval depending on other operational factors phospholipid vesicles may act as carriers for therapeutic and may identify regions of host response to tumor antigen and agents. possibly even circumstances unfavorable for neoplastic prolif Goldenberg ef a/. (16) have reported a technique for tumor eration. detection and localization by external photoscanning using radiolabeled antibodies to carcinoembryonic antigen adminis Conclusion tered i.v. The feasibility of raising antibodies to tumor markers, which may subsequently be radiolabeled, would confer re It is inevitable that diagnostic modalities must not only be markable specificity upon current detection methods, provided directed at confirming the presence of morphologically recog such agents retain their unique immunological properties. Af nizable neoplasm, but they must also anticipate detecting con finity for such labeled antibodies administered i.v. or intersti- ditions within the host which may precede, predispose to, or preclude the establishment of a neoplasm in a particular bio

Table 1 logical environment. Correlation of internal mammary lymphoscintigram with pathological stage in Since components of the immune system, including tissue 10 72 patients with breast carcinoma (8) macrophages and the sinus histiocytes within the lymph node, (%)StageIIIIIIIVUnstagedNo. Lymphoscintigram results play an essential role in the transport, lymphatic distribution, and retention of radiocolloid, variations in these parameters of pa tients21350514628180Normal6554212829Suspicious16171989Abnormal1625576560Equivocal1212Absent222 have the potential of reflecting alterations in the immunological expression of the host organism. With the availability of different approaches, it is apparent that many facets of the host-tumor interaction may yet be evaluated, and all data must be viewed carefully to ensure that Reproduced with permission from International Journal ol Radiation Oncol further dimensions to this diagnostic process are not over ogy, Biology and Physics. 2: 755-761. 1977. Pergamon Press, Ltd. looked.

Table 2 Percentage of treatment failure related to axillary and parasternal lymphatic involvement (9)"

Follow-upperiod(yr)Evidence ofdisease -IM,0 -AX -IM, -(-AX + IM, -AX -HIM, +AX

Princess Margaret Hospital: 439 85(19r 13/146(9) 37/175(21) 6/28(21) 29/90 (32) patients; axillary histology; parasternal lymphoscintigraphy

Livingston e( al. (21): 373 patients; 130(32) 29/204 (14) 50/104 (48) 7/15(47) 34/50(68) axillary and parasternal histology Reproduced by permission of the editors of Clinical Radiology. IM, internal mammary lymphoscintigraphy or histology; AX, axillary histology. c Numbers in parentheses, percentage.

3070 CANCER RESEARCH VOL. 40

Acknowledgments 15. Fisher, E. R., and Fisher, B. Role of regional lymph nodes. In: B. A. Stoll (ed.), New Aspects of Breast Cancer, Vol. 3. pp. 45-59. Great Britian: I wish to acknowledge the assistance of A. Warbick-Cerone in obtaining the William Heineman Medical Book Publications, 1977. experimental data in rabbits and of M. Moore in preparation of the manuscript. 16. Goldenberg. D. M., DeLand, F.. Kim, E.. Bennett. S., Primus. F. R., van Nagell. J. R.. Jr., Estes, N., DeSimone, P., and Rayburn, P. Use of radiola- References beled antibodies to carcinoembryonic antigen for the detection and locali zation of diverse cancers by external photoscanning. N. Engl. J Med., 298 1. Arnaud. D.. Dilhuydy. J. M.. Basse-Cathalinat, B., Ducassou, D., and Blan- 1384-1388, 1978. quet. P. Exploration des chaÃ®nesmammaires internes au moyen de la 17. Jackson. F. R., Bowen, P.. and Lentie. B. C. Scintilymphangiography with lymphographie isotopique. J. Fr. Biophys. Med NucÃ, 2. 99-104. 1977. MmTc-antimony sulphide colloid in hereditary lymphedema (Nonne-Milroy 2. Boak, J. L., and Agwunobi. T. C. A study of technetium-labelled sulphide disease). Clin NucÃ.Med.. 3 296-298. 1978. colloid uptake by regional lymph nodes draining a tumour-bearing area. Br. 18. Jackson, F. R., and Lentie. B. C. The scintilymphangiographic 'flare sign J. Surg.. 65. 374-378. 1978. of lymphangitic obstruction. Clin. NucÃ Med . 2. 211-213. 1977. 3. Bronskill. M. J., Bush, R S., and Ege, G. N. A quantitative measurement of 19. Kaplan. W. D., Davis, M. A., and Rose, C. M. A comparison of two techne- peritoneal drainage in malignant ascites. Cancer (Phila.), 40: 2375-2380. tium-99m labeled radiopharmaceuticals for lymphoscintigraphy: concise 1977. communication J. NucÃ.Med.. 20: 933-937, 1979. 4. Bronskill. M. J., Harauz. G., and Ege. G. N. Computerized internal mammary 20. Levy, M. H., and Wheelock, E. F. The role of macrophages in defense lymphoscintigraphy in radiation treatment planning of patients with breast against neoplastic disease. Adv. Cancer Res.. 20. 131-163. 1974. carcinoma. Int. J. RadiÃ¢t.Oncol Biol. Phys.. 5. 573-579, 1979. 21. Livingston. S. F.. and Arien, M. The extended extrapleural radical mastec 5. Davidson, J. W.. and Hobbs. B. B. The lymphatic microcirculatory spaces in tomy: its role in the treatment of carcinoma of the breast. Ann. Surg., / 79. lymph nodes during an immune response. Invest. Radiol.. 9 32-36, 1974. 260-265. 1974. 6. Dufresne, E. N., Kaplan. W. D., and Zimmerman, R. E. The application of 22. Matsuo. S. Studies on the metastasis of breast cancer to lymph nodes. II. internal mammary lymphoscintigraphy to radiation therapy planning. J. NucÃ. Diagnosis of metastasis to internal mammary nodes using radiocolloid Acta Med., in press. 1980. Med. Okayama. 28. 361-371, 1974 7. Ege, G. N. Internal mammary lymphoscintigraphyâ€”the rationale, technique, 23. Munzenrider. J. E.. Tchakarova, I., Castro. M.. and Carter. B. Computerized interpretation and clinical application: a review based on 848 cases. Ra body tomography in breast cancer. Cancer (Phila.). 43: 137-150. 1979. diology. 118: 101-107, 1976. 24. Osborne. M. P., Jeyasingh, K.. Richardson. V J.. Vincenti. A. C.. Jewkes. 8. Ege, G. N. Internal mammary lymphoscintigraphy in breast carcinoma: a R. F., and Burn, J. I. The detection of lymph node mÃ©tastases using study of 1072 patients. Int. J. RadiÃ¢t.Oncol Biol. Phys . 2 755-761. 1977. radiolabelled colloids. Br. J. Surg.. 65. 354-371, 1978. 9. Ege, G. N. Internal mammary lymphoscintigraphy: a rational adjunct to the 25. Osborne, M. P., Richardson, V. J., Jeyasingh. K.. and Ryman, B. Radionu staging and management of breast carcinoma. Clin. Radiol.. 29 453-456. clide labelled liposomesâ€”a new lymph node imaging agent Int. J. NucÃ. 1978. Med Biol.. 6 75-83. 1979. 10. Ege, G. N. Lymphoscintigraphy. In: Sir T. Symington, A. E. Williams. J. G. 26. Prassvinichai, T. H., Nedwich, A., Lam, S., and Brady. L W Observations McVie (eds.). Proceedings of Tenth Pfizer International Symposium: Cancer- on the transport mechanism of colloidal gold. Radiol. Clin. Biol.. 42: 460- Assessment and Monitoring. Edinburgh: Churchill Livingstone, 1980. 467, 1973. 11. Ege, G. N. Radiocolloid lymphoscintigraphy. In: M. Viamonte and A. Rutti- 27. Sage, H.. and Gozun, B. Lymphatic scintigrams: a method for studying the mann (eds.). Atlas on Lymphography. Stuttgart. New York: Georg Thieme functional pattern of lymphatics and lymph nodes. Cancer (Phila.). / /: 200- Verlag, 1980. 203, 1958. 12. Ege. G N., and Warbick. A. Lymphoscintigraphy: a comparison of "Teâ„¢ 28 Seaman. W.. and Powers. W. E. Studies on the distribution of radioactive antimony sulphide colloid and "Teâ„¢ stannous phytate. Br. J Radiol . 52. colloidal gold in regional lymph nodes containing cancer. Cancer (Phila.). 8. 124-129, 1979. 1044-1046, 1955. 13. Ege, G. N., Warbick-Cerone, A., and Bronskill, M. J. Radionuclide lympho 29. Thomas, G. G. Lymphatic dissemination of radiogold in the presence of scintigraphyâ€”an update. In: Proceedings of the Second International Sym lymph node mÃ©tastases.Surg. Gynecol Obstet , 193. 51-56. 1956. posium on Radiopharmaceuticals. Seattle, March 18 to 23. 1979. New York: 30. UICC. TNM Classification of Malignant Tumors. Geneva: Union Internationale The Society of Nuclear Medicine. Inc.. 1979. Contre de Cancer, 1978. 14. Fidler, l. J., Gersten. D. M.. and Hart, I. R. The biology of cancer invasion 31. Wallace, I. W. J., and Champion. H R. Axillary nodes in breast cancer and metastasis. Adv. Cancer Res., 28 149-250. 1978. Lancet, 1: 217-218, 1972.

AUGUST 1980 3071

Günes N. Ege

Cancer Res 1980;40:3065-3071.

Updated version Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/40/8_Part_2/3065

E-mail alerts Sign up to receive free email-alerts related to this article or journal.

Reprints and To order reprints of this article or to subscribe to the journal, contact the AACR Publications Subscriptions Department at [email protected].

Permissions To request permission to re-use all or part of this article, use this link http://cancerres.aacrjournals.org/content/40/8_Part_2/3065. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC) Rightslink site.