[CANCER RESEARCH 40, 3065-3071. August 1980] 0008-5472/80/0040-0000$02.00 Radiocolloid Lymphoscintigraphy in Neoplastic Disease1 GuneçN. 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 ¡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 3ß). ' 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 Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1980 American Association for Cancer Research. G. N. Ege 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 métas 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 ¿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 £ 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 Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1980 American Association for Cancer Research. Lymphoscintigraphy in Neoplastic Disease 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