Assessment of the potential uses of liposomes for lymphoscintigraphy and lymphatic drug delivery failure of 99m-technetium marker to represent intact liposomes in lymph nodes

The in vivo fate of subcutaneously injected neutral SUV liposomes in rats was examined using a membrane marker, ^99mTc, and an aqueous marker, ¹²⁵I-labelled poly(vinyl pyrrolidone). Liposomes with entrapped ¹²⁵I-labelled poly(vinyl pyrrolidone) were labelled with ^99mTc by the SnCl₂ method [2]. ^99mTc-radioactivity was localized several-fold more in the primary and secondary regional lymph nodes than ¹²⁵I-labelled poly(vinyl pyrrolidone)-radioactivity. Similarly, ^99mTc-radioactivity appeared and was subsequently cleared from the circulation much more rapidly than ¹²⁵I-labelled poly(vinyl pyrrolidone). The gel chromatography of the lymph node homogenate revealed that 60–70% of ¹²⁵I-labelled poly(vinyl pyrrolidone)-radioactivity was in the liposome fractions, whereas only 3% of ^99mTc-radioactivity was co-eluted with liposomes. Thus, the two markers have different fates in the lymphatics, and the presence of all ^99mTc-radioactivity does not represent the 60–70% of intact liposomes present in lymph nodes. Using the aqueous marker ¹²⁵I-labelled poly(vinyl pyrrolidone), the lymphnode localization of positive, negative and neutral small unilamellar vesicles was studied, and it was found that ¹²⁵I-radioactivity was more localized from negative liposomes than from positive liposomes, which in turn was more localized than that from neutral liposomes. Thus, these findings differ from those reported earlier [2], where the authors used ^99mTc as a liposomal marker. In vitro studies showed that liposomes of preparations containing 20 mol% cholesterol became ‘leaky’ to low-molecular-weight drugs, for example, methotrexate (M_r 454) to a much greater extent than with a large-molecular-weight substance, ¹²⁵I-labelled poly(vinyl pyrrolidone) (M_r 30 000–40 000), when incubated with rat lymph at 37°C. Using the two markers ^99mTc and ¹²⁵I-labelled poly(vinyl pyrrolidone) it was found that the localization of both radioactivities was reduced in lymph nodes draining λ-carrageenan-treated footpads. In conclusion, it is suggested that liposomes can be used for the delivery of drugs to diseased lymph nodes, and it would be worthwhile examining the possibilities of using alternative methods of labelling liposomes with ^99mTc rather than using the SnCl₂ technique [2], or using other radionuclides as markers for γ-scan imaging.     

Étude de faisabilité du ganglion sentinelle dans le cancer de la prostate par cœlioscopie : premiers résultats

Objectives

The standard lymphadenectomy is currently a challenge in the management of prostate cancer. The aim of this prospective study was to evaluate the performance of the sentinel lymph node (SLN) by laparoscopy in patients with localized prostate cancer, candidates for local treatment.

Patients and methods

Patients were injected transrectal ultrasound-guided with 0.3 mL/100MBq 99^mTc-Sulfur rhenium colloid in each prostatic lobe, the day before surgery. Lymphoscintigraphy was performed after 2 hours. The detection was realized intraoperatively with a laparoscopic probe (Gamma Sup Clerad^®) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by HPS staining and followed by immunochemistry if SLN was free.

Results

Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases (D’Amico), PSA median 9.5 ng/mL [6–130], were included in the study. The lymphoscintigraphic detection rate was 94.2% (66/70) and intraoperative of 97.0% (68/70). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14.0%). The internal iliac region is the first metastatic site (40.9%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59.0% of lymph node metastases.

Conclusion

The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limits the risk of surgical extended dissection while maintaining the accuracy of the information.     

Indirect Magnetic Resonance Imaging Lymphography Identifies Lymph Node Metastasis in Rabbit Pyriform Sinus VX2 Carcinoma Using Ultra-Small Super-Paramagnetic Iron Oxide

Background

USPIO is a contrast agent for MRI that can generate T2W images with low signal intensities. After subcutaneous or intravenous injection of USPIO, normal lymph node tissues uptake these nano-particles, but tumor cells do not. Thus, tumor metastasis can be detected using this contrast agent.

Objective

The aim of this study was to access the feasibility of USPIO enhanced MRI for the detection of cervical lymph node metastasis in a pyriform sinus carcinoma animal model and to investigate the ability of USPIO to enhance images of cervical lymph node metastases.

Methods and Findings

Twenty New Zealand rabbits were randomly divided into tumor and inflammatory groups, and each group contained 10 rabbits. In the inflammatory group, a 0.5 ml egg yolk emulsion was injected into the sub-mandibular muscle of the rabbits to induce an inflammatory reaction in their cervical lymph nodes. In the tumor group, a VX2 tumor tissue suspension was transplanted into the pyriform sinus sub-mucosa of the rabbits using direct laryngoscope. Four weeks after the tumor or egg yolk injection, MRIs were performed before and after USPIO injection to observe the imaging enhancement features of USPIO. After that, a histo-pathological analysis was performed for all rabbits. We found the metastatic lymph nodes had no signal reduced intensity or irregular signal reduced intensity on T2-weighted image by using USPIO enhancement. In the tumor group,the sensitivity and specificity of plain MRI were 57.6% and 60.7%. The corresponding values of USPIO-enhanced MRl were 96.1% and 85.7%. (P<0.05)

Conclusion

The features and the extent of the lymph node metastases corresponded to those observed on USPIO-enhanced MR images. USPIO-enhanced MRI is useful for the detection and estimation of lymph node metastasis in this cervical carcinoma animal model.     

Distinctions between rabbit lymph node cell populations responding to primary and secondary injections of keyhole limpet hemocyanin

Rabbits were injected once or twice into the hind foot pads with alum-precipitated keyhole limpet hemocyanin. At the height of the primary or secondary responses individual rabbits were sacrificed for the preparation of lymph node cell suspensions from the regional lymph nodes. These cells were employed for the in vitro study of antibody synthesis by the incorporation of ¹⁴C-leucine and the secretion of antibody by the time of appearance of radioactive antibody in the medium. The primary response cells rapidly synthesized and secreted IgM and IgG antibodies. The secondary response cells rapidly synthesized IgM and IgG antibodies, secreted IgG antibody promptly, but secreted the IgM antibody with a lag of six to ten hours. Microsomal fractions could not be prepared from the primary response cells, but were readily produced from the cells of the secondary response. The primary response cells contained mainly free ribosomes, those of the secondary response predominantly membrane-bound ribosomes. It was postulated that IgM antibody was not secreted until it was glyco-sylated in the Golgi apparatus and that the lag in secretion entailed the time for this rate-limiting step to occur.     

99mTc-CD19 monoclonal antibody is not useful for imaging of B cell non-Hodgkin’s lymphoma

 In this study we investigated the applicability of ^99mTc-labeled CD19 monoclonal antibody (mAb) for tumor imaging in patients with B cell non-Hodgkin’s lymphoma. A 1-mg sample of murine CD19 mAb was labeled with approximately 550 MBq [^99mTc]pertechnetate. The labeled mAb was administered i. v. to seven patients, four without and three with pretreatment with 10 mg unlabeled CD19 mAb. The number of circulating B cells was decreased by 44±5% 1 h after injection of the radiolabeled mAb. Peripheral B cells were coated with CD19, resulting in partial modulation of CD19, most pronounced in the three pretreated patients. Whole-body images were obtained with a gamma camera and compared with results obtained by conventional imaging techniques. Initially, blood-pool activity dominated, whereas 24 h after injection the radioactivity was mainly located in the spleen, kidneys and liver. In two patients, a lesion in the spleen appeared as an unlabeled spot. In one patient, a lesion in the femur, which was detected by computed tomography (CT) and gallium-67 scans, was also seen on the CD19 scan from 1 h after administration of the radioimmunoconjugate onwards. Good imaging of bone marrow infiltration was observed in one of three patients. Lymph node involvement was not observed in any of the patients in whom affected lymph nodes were detected by CT or gallium-67 scan. In conclusion, in the present study radioimmunodetection with ^99mTc-labeled CD19 mAb was found to be inferior to CT and gallium-67 scanning in the diagnosis of patients with B cell non-Hodgkin’s lymphoma. Received: 14 March 1996 / Accepted: 14 May 1996     

99mTc标记BmK CT及其胶质瘤荷瘤裸鼠的SPECT成像研究

目的:通过放射性核素~(99m)Tc标记BmK CT多肽制备靶向胶质瘤的显像剂,探讨~(99m)?Tc-BmK CT用于胶质瘤显像的可行性。方法:采用BmK CT多肽游离的氨基与DTPA酸酐反应得到BmK CT-DTPA,经99m Tc标记后通过柱层析分离纯化制备~(99m)?Tc-BmK CT。测定标记物在PBS溶液和血清中不同时间点放射性化学纯度,评价BmK CT-~(99m)?Tc体外稳定性。新西兰白兔耳缘静脉注射~(99m)Tc-BmK CT进行SPECT显像,观察不同时间点体内的放射性分布。皮下胶质瘤裸鼠经尾静脉注射~(99m)Tc-BmK CT,观察不同时间点肿瘤的摄取情况;注射后4 h处死裸鼠,分离肿瘤和主要器官进行离体SPECT显像,并用勾画感兴趣区法分析相对放射性计数。结果:~(99m)Tc标记BmK CT多肽标记率大于80%,经柱层析分离纯化后放射性化学纯度大于99%。标记物在PBS和血清稳定性良好,6 h内放射性化学纯度均大于95%,12 h内放射性化学纯度大于90%。正常白兔SPECT显像表明~(99m)Tc-BmK CT主要浓聚在肝脏、脾脏和肾脏,软组织持续显影微弱,甲状腺区及胃肠未见核素浓聚;显像剂主要通过泌尿系统排泄,24 h肾脏与肝脏显影接近。胶质瘤裸鼠SPECT显像表明,注射后4 h肿瘤显像清楚,ROI分析结果显示肿瘤/肌肉比4.26±0.25,标记物在肿瘤内代谢缓慢,8 h肿瘤部位仍有较高摄取。结论:本研究成功制备了~(99m)Tc标记BmK CT多肽,标记物主要被肝、脾和肾摄取,经泌尿系统排泄;~(99m)Tc-BmK CT能够在皮下胶质瘤中浓聚,注射后4 h肿瘤显影清晰,瘤内代谢缓慢,有潜力成为一种新型胶质瘤分子探针。     

FOXP3+ Lymphocyte Density in Pancreatic Cancer Correlates with Lymph Node Metastasis

Objective

To determine if the density of FOXP3⁺ lymphocytes in primary tumors and lymph nodes in pancreatic cancer correlates with the presence of lymph node metastases.

Methods

FOXP3⁺ lymphocyte density in primary pancreatic cancer tissue and draining lymph nodes was measured using immunohistochemistry. We analyzed the clinical and pathological aspects associated with the accumulation of FOXP3⁺ lymphocytes in pancreatic cancer. We also analyzed the correlation of density of FOXP3⁺ lymphocytes in lymph nodes with the nodal status and distance from the primary tumor.

Results

FOXP3⁺ lymphocyte density in pancreatic cancer was significantly higher than in paratumoral pancreatic tissue. The density of FOXP3⁺ lymphocytes in local tumor tissue correlated significantly with the histological grade and overall lymph node status. Furthermore, FOXP3⁺ lymphocyte density was significantly higher in positive lymph nodes than in negative ones, while it had no correlation with the distance of the lymph node from the primary tumor.

Conclusion

FOXP3⁺ lymphocyte density in primary tumor tissue in patients with pancreatic cancer correlates with lymph node metastasis. Lymph nodes containing metastases having higher FOXP3⁺ lymphocyte densities than do negative lymph nodes.     

Properties of multilamellar liposomes containing 99mTcO−4: Effect of distearoylphosphatidylcholine to sphingomyelin ratio

Multilamellar liposomes composed of eight different mixtures of distearoylphosphatidylcholine (DSPC) and sphingomyelin (SM) were prepared containing [^99mTc]pertechnetate. The in vitro permeability of the liposome preparations in buffer and serum were measured by both dialysis and direct exposure. Liposomes composed of 25–33% SM were least permeable exhibiting leakage half-times of approximately 70 h in buffer and 52 h in serum. Pertechnetate-containing liposomes of three different lipid compositions were injected into mice and the biodistribution of ^99mTc activity was determined. All preparations were taken up primarily by the lungs and liver. The half-time for clearance of ^99mTc activity ranged from 24.8 to 30.6 h for the liver and 25.3 to 33.0 h for the lungs.     

Role of serum albumin as a carrier of 99mTc-complex to tumor tissue

To elucidate a factor required for tumor-imaging ^99mTc-labeled radiopharmaceuticals, in vivo behaviors of ^99mTc-l-cysteine (^99mTc-Cys) and ^99mTc-2-mercaptoethylamine (^99mTc-ME) were compared with that of ^99mTc-dl-homocysteine (^99mTc-Hcy) which had been found to accumulate in several experimental tumors. When these three complexes were intravenously injected into mice bearing Ehrlich solid tumor, their tumor affinity was found to depend on their binding ability to serum albumin; ^99mTc-Hcy, the albumin-binding ability of which was highest of the three, was the most tumor-tropic. When the albumin-bound complexes of these three were injected, their tumor distributions were enlarged. These results suggest the importance of serum albumin in serving as a carrier for the transport of ^99mTc-Hcy-related compounds to tumor tissue.     

Lymphocyte traffic through granulomas: Differences in the recovery of indium-111-labeled lymphocytes in afferent and efferent lymph

Afferent lymphatics draining granulomas and efferent lymphatics from normal and stimulated lymph nodes were cannulated in sheep. There was a greatly increased output of cells in afferent lymph-draining chronic inflammatory sites or Freund's adjuvant-induced granulomas. Cells collected from these lymphatics were radiolabeled with ¹¹¹In and injected intravenously. The reappearance of these labeled cells in lymph at various sites was measured. Labeled afferent lymph cells migrated from blood through the granuloma back into afferent lymph in large numbers and with kinetics which were comparable to efferent lymphocytes recirculating through a lymph node. When labeled afferent lymph cells were injected the specific activity (cpm/10⁷ cells) in afferent lymph was five times higher than that in efferent lymph from a normal node. When efferent lymph cells were labeled the afferent lymph specific activity was one-half that in efferent lymph. It is suggested that the cells in afferent lymph migrate preferentially from blood through the granuloma and constitute a unique population of cells.     

Experimental allergic encephalomyelitis: changes in growth and proliferation within the draining lymph node following injection of basic encephalitogenic protein in Freund's complete adjuvant

Changes in wet weight, dry mass, and DNA synthesis of draining lymph nodes from rats injected with encephalitogenic basic protein in Freund's complete adjuvant (FCA) were studied. Lymph nodes of rats injected with encephalitogenic basic protein in FCA show accelerated enlargement from the second up to the fourth day after injection, as compared to lymph nodes of rats injected with FCA alone, or with nonencephalitogenic basic protein in FCA. The greatest difference in lymph node weight was found on the fourth day. At this time cell division is higher in the group injected with encephalitogenic protein in FCA than in the group injected with FCA alone. However, the increased division of cells in situ cannot account, in and by itself, for the enlargement of the lymph node which was observed. It is concluded that migration of lymphocytes into the lymph node makes a substantial contribution to the hyperplasia of the lymph node.The results suggest that accelerated lymph node enlargement may be specific, at least in part, for induction of experimental allergic encephalomyelitis.     

Natural cytotoxicity in rats: Radiation-induced changes in the early killing of allogeneic cells

In some strain combinations among inbred tats intravenously injected ⁵¹Cr-labeled lymphocytes are rapidly destroyed in substantial numbers by unsensitized allogeneic hosts. This phenomenon has been referred to as natural cytotoxicity (NC) and is characterized by decreased lymph node radioactivity, increased kidney and urine radioactivity, and to a lesser extent increased liver radioactivity in allogeneic hosts, when compared with the distribution of label in syngeneic recipients of the same cell suspension. A single exposure to 800 rad either 1 or 7 days before the injection of ⁵¹Cr-labeled lymphocytes effected a reduction in NC as defined by all the above parameters in a strain combination exhibiting high NC. The same dosage of radiation abolished NC in a strain combination exhibiting intermediate → low NC. Because NC was not always completely abolished, the phenomenon was held to be partially radiosensitive. An increased accumulation of ⁵¹Cr-labeled lymphocytes was seen in the lymph nodes of both syngeneic and allogeneic irradiated hosts when compared with nonirradiated controls, although the increase was greater in allogeneic than in syngeneic hosts. This increased colonization in the lymph nodes of irradiated hosts seemed unlikely to be due to an increase in the available “space” in the lymph nodes following irradiation.     

Use of liposomes as carriers for radiation synovectomy

Using [^99mTc]pertechnetate as an aqueous space marker, the permeability of liposomes composed of seven different mixtures of distearoylphosphatidylcholine (DSPC) and sphingomyelin (SM) was determined. Liposomes containing 20–33% SM were the least permeable in the presence of rheumatoid synovial fluid. Following injection of ^99mTc-containing liposomes into the knee joints of rabbits, retention of ^99mTc in the knee was more than 200 times greater than following injection of nonencapsulated [^99mTc]pertechnetate. The knee clearance biologic half time of ^99mTe with DSPC/SM (4:1) liposomes was 64 h. Most of the activity that had leaked from the knee was not found in extra-articular tissues, suggesting rapid excretion. When DSPC/SM (4:1) liposomes were labeled with ¹¹¹In(oxine), a knee clearance biologic half time of greater than 1200 h was observed.     

Activation and route of administration both determine the ability of bone marrow-derived dendritic cells to accumulate in secondary lymphoid organs and prime CD8<Superscript>+</Superscript> T cells against tumors

Aims

To examine the effects of route of administration and activation status on the ability of dendritic cells (DC) to accumulate in secondary lymphoid organs, and induce expansion of CD8⁺ T cells and anti-tumor activity.

Methods

DC from bone marrow (BM) cultures were labeled with fluorochromes and injected s.c. or i.v. into naïve mice to monitor their survival and accumulation in vivo. Percentages of specific CD8⁺ T cells in blood and delayed tumor growth were used as readouts of the immune response induced by DC immunization.

Results

The route of DC administration was critical in determining the site of DC accumulation and time of DC persistence in vivo. DC injected s.c. accumulated in the draining lymph node, and DC injected i.v. in the spleen. DC appeared in the lymph node by 24 h after s.c. injection, their numbers peaked at 48 h and declined at 96 h. DC that had spontaneously matured in vitro were better able to migrate compared to immature DC. DC were found in the spleen at 3 h and 24 h after i.v. injection, but their numbers were low and declined by 48 h. Depending on the tumor cell line used, DC injected s.c. were as effective or more effective than DC injected i.v. at inducing anti-tumor responses. Pre-treatment with LPS increased DC accumulation in lymph nodes, but had no detectable effect on accumulation in the spleen. Pre-treatment with LPS also improved the ability of DC to induce CD8⁺ T cell expansion and anti-tumor responses, regardless of the route of DC administration.

Conclusions

Injection route and activation by LPS independently determine the ability of DC to activate tumor-specific CD8⁺ T cells in vivo.

     

Comparative studies of radiocitrates in oncological models—I. 99mTc citrate and 67Ga citrate uptake by EMT-6 tumors in mice

⁶⁷Ga citrate and ^99mTc citrate (Solcocitran) were injected sequentially, with an interval of 48 h, into Balb/c mice bearing transplanted EMT-6 tumors. Tissue distributions of ⁶⁷Ga and ^99mTe were measured simultaneously at intervals of 1, 3, 5 and 8 h after injection of the ^99mTc citrate (49, 51, 53 and 56 h after ⁶⁷Ga citrate). Maximal tumor:blood ratios for ^99mGa and ^99mTc were 13.8 ± 3.2 and 4.0 ± 1.0 respectively, both occurring at the final period. The maximum tumor index (T.I. = T:B x % dose/g) for ⁶⁷Ga was 71 ± 23% 56 h after injection, and for Tc was 13 ± 12% 1 h after injection. Liver, kidney and spleen had equal or higher concentrations of radioactivity than tumor for either radiotracer. The somewhat higher tumor:blood ratio for ⁶⁷Ga citrate was offset by the time required for this optimum to be reached. Alternatively, the best ^99mTc citrate tumor:blood ratios were attained within 8 h, with less liver and gut radioactivity. These data fall within the range of results from other clinical and animal model studies of ⁶⁷Ga citrate and Tc citrate. In view of the radiation dose, the inconvenience of the 48–72 h wait, and the cost of ⁶⁷Ga, and because neither radiopharmaceutical is tumor specific, ^99mTc citrate may have a place in early oncological screening. The results are discussed as part of a comprehensive review of the ^99mTc citrate literature.     

Comparison of three RE agents—99mTc-phytate, 99mTc-sulfur colloid and 99mTc-Sb2S3 colloid in the rodent species

^99mTc-phytate, ^99mTc-sulfur colloid and ^99mTc-antimony sulfide colloid are recognised as RE agents in clinical nuclear medicine. Since these three agents exist in vitro in different forms of particulate aggregation it was of interest to compare their properties and to evaluate the merits and limitations of each of these agents. A comparison was carried out in rats and rabbits as a prelude to a systematic study in human subjects. Quality tested radiopharmaceuticals were prepared and their pharmacokinetics studied in rats. The blood clearance, tissue distribution and scinti-imaging patterns of the RE system were also compared in rabbits. All the agents have excellent localizing properties in the liver but differ in varying extents in their disposition in other tissues. ^99mTc-sulfur colloid has some predisposition for the lungs while ^99mTc-phytate has a little propensity for the kidney and gut at late time periods. ^99mTc-Sb₂S₃ colloid shows a more pronounced concentration in the bone-marrow, and displays intermediate properties between ^99mTc-phytate and ^99mTc-sulfur colloid, besides being the most stable (in vitro) radiopharmaceutical in this series of RE agents.     

Analysis of elimination mechanisms of some 99mTc-complexes

The biological behaviour of complexes of ^99mTc with aminopolycarboxylic and aminocarbohydroxamic ligands EDTA (ethylenediaminetetraacetic acid), DTPA (diethylenetriaminepentaacetic acid), EDTAH (ethylenediaminetetraacetohydroxamic acid) and HIDAmH (N-2-hydroxyethyl-N-carboxymethyl-aminoacetohydroxamic acid) was studied in rabbits. The pharmacokinetic parameters determined in intact rabbits were compared with the results obtained in the study of renal and hepatic clearance of the complexes under study. Hepatobiliary excretion, which in [^99mTc]EDTA forms 20–30% of the total excreted amount, is of negligible magnitude in the other ^99mTc-complexes studied (<2%). Their renal clearance is not influenced by the inhibition of tubular secretion with probenecid. Binding to plasma proteins increases in the order [^99mTc]DTPA < [^99mTc]EDTA <[^99mTc]HIDAmH <[^99mTc]EDTAH and the elimination half-life increases in the same order. The value of renal clearance of the complexes studied related to inulin clearance correlates well with the fraction of the free drug in the plasma. In rabbits the complexes under study are excreted mainly by the mechanism of glomerular filtration in the kidney.     

Assessing good operating conditions for intraoperative imaging of melanoma sentinel nodes by a portable gamma camera

ObjectiveTo provide guidance for reliable identification of low-activity sentinel nodes in the setting of melanoma surgery using a commercial hand-held gamma camera.MethodsThe average uptake of ^99mTc nanocolloid by sentinel nodes was evaluated in 95 excised nodes using a Sentinella 102^® (Oncovision, Valencia, Spain) portable gamma camera. The device sensitivity was assessed for different source depths and collimator distances, imaging an 8-mm sphere filled with a known-activity solution of ^99mTc. Five nuclear medicine physicians were asked to identify the source at different activity levels and positions within the field of view. For each image the number of signal counts inside a circular region of interest (ROI) was measured, while the variability of ROI counts among operators was assessed. The number of counts providing a minimal, near-constant inter-operator variability was determined as a criterion for a consistent identification of the source. Either the minimum activity or the acquisition time needed to collect the appropriate statistics were then calculated.ResultsThe median SN uptake (0.5%) turned out to be compatible with values reported in the literature. The sensitivity of the compact gamma camera ranged from ∼25 cpm/kBq to ∼1 cpm/kBq. A total of 50 counts in the ROI circumscribing the lymph node-simulating sphere appeared to be a robust criterion for identification of the source.ConclusionsTen megabecquerels of injected activity at the time of surgery and one minute of acquisition allows reliable identification of sentinel nodes for collimator-to-source distances up to 10 cm.     

Three stage axillary lymphatic massage optimizes sentinel lymph node localisation using blue dye

Aims

This paper describes a simple technique of axillary and breast massage which improves the successful identification of blue sentinel nodes using patent blue dye alone.

Methods

Patent blue dye was injected in the subdermal part of the retroaroelar area in 167 patients having surgical treatment for invasive breast cancer. Three stage axillary lymphatic massage was performed prior to making the axillary incision for sentinel lymph node biopsy. All patients had completion axillary sampling or clearance.

Results

A blue lymphatic duct leading to lymph nodes of the first drainage was identified in 163 (97%) of the patients. Results are compared with 168 patients who had sentinel lymph node biopsy using blue dye without axillary massage. Allergic reactions were observed in four patients (1.2%).

Conclusion

Three stage axillary lymphatic massage improves the successful identification of a blue sentinel lymph node in breast cancer patients.