Sentinel lymph node mapping of breast cancer via intradermal administration of Lymphoseek

https://doi.org/10.1016/j.nucmedbio.2007.05.003Get rights and content

Abstract

Lymphoseek is a molecular imaging agent specifically designed for sentinel lymph node (SLN) mapping. We conducted a Phase I trial which measured the injection site clearance and SLN accumulation after a single intra dermal injection of Lymphoseek or [99mTc]sulfur colloid protocol. Ten patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of 99mTc-labeled Lymphoseek and five patients received an intradermal administration of filtered [99mTc]sulfur colloid (fTcSC). Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than fTcSC. The mean Lymphoseek clearance half-time was 2.61±0.72 h compared to 24.1±17.7 h for fTcSC. The mean SLN uptake of Lymphoseek (1.1±.5%) and fTcSC (2.5±4.9%) was statistically equivalent (P=.28). When an intra dermal injection was employed, Lymphoseek demonstrated faster injection site clearance than fTcSC.

Introduction

Lymphoseek is a molecular imaging agent specifically designed for sentinel lymph node (SLN) mapping. The technetium-99m-labeled radiopharmaceutical attains rapid clearance from the injection site by virtue of its small molecular diameter [1]. In rabbits, Lymphoseek exhibited significantly faster injection site clearance than technetium-99m sulfur colloid [1]. Submucosal administration into pig colon and stomach resulted in lymph node accumulation within 10 min [2], [3], [4]. Rapid SLN uptake was also observed after direct injection into the porcine prostate gland [5]. The molecular structure of Lymphoseek contains the carbohydrate mannose which provides the radiopharmaceutical with a high affinity [1] for a receptor, mannose binding protein [6], which is specific to lymphoid tissue. This molecular feature provides Lymphoseek with sustained SLN uptake without distal lymph node accumulation, a property demonstrated in rabbit [1] and pig [2] studies.

Clinical trials of Lymphoseek also demonstrated rapid injection site clearance compared with filtered technetium-99m-labeled sulfur colloid and sustained SLN uptake. In women with breast cancer, Lymphoseek demonstrated significantly faster clearance from the injection site and equivalent SLN accumulation [7]. No adverse events or clinically significant changes in clinical and laboratory values were observed. These findings were also demonstrated at the 5-nmole dose level [8] and by patients with melanoma [9].

We present the injection site clearance and SLN accumulation after a single intradermal injection of Lymphoseek or filtered [99mTc]sulfur colloid (fTcSC) which employed a protocol for SLN mapping of breast cancer. Our previous studies employed paratumoral/intradermal technique where the injection of the radiopharmaceutical was initiated paratumorally and finished with the needle in the intradermal position.

Section snippets

Patient enrollment

Ten female patients with breast cancer who would normally be offered SLN biopsy as per University of California, San Diego, guidelines participated in this study. We entered women who presented a challenge to successful SLN mapping and lymphoscintigraphy; at least one of the following criteria was required: (1) over 60 years old, (2) having a nonpalpable lesion or (3) having an upper-outer quadrant lesion. The need to have follow-through node dissection was determined by pathologic outcome of

Results

Table 1 lists the subject number and age. The table also lists the tumor diagnosis, size, stage and location. Also listed are the agent and the amount of radioactivity administered. Table 2 lists the subject number, radiopharmaceutical, the injection site clearance rate constant and half-life, the time at which the SLN was excised relative to the time injected. Also listed is the probe count rate after excision of each SLN as defined by the radiotracer or blue dye. Entries for Subjects 1 and 5

Discussion

This study demonstrated significantly faster injection site clearance by Lymphoseek than fTcSC. Contrary to our expectation, the intradermal administration did not exhibit a faster clearance half-life (2.62±0.55 h) than Phase I study group that utilized a peritumoral/intradermal injection [7], which exhibited a clearance half-life of 2.72±1.57 h. This was also true for our melanoma study [9], where the measured clearance half-life was 2.05±0.89 h. One noticeable difference between the three

Conclusion

When a single intradermal injection is employed, Lymphoseek demonstrated significantly faster injection site clearance than fTcSC. The injection site clearance rate and SLN accumulation were comparable to clearance and accumulation of Lymphoseek after intradermal or intradermal/peritumoral administration to melanoma or breast cancer patients.

Acknowledgments

This work was supported by grant R21-CA09764 of the Quicktrials Program of the National Cancer Institute. We thank Dr. Ernest V Belezzuoli, MD, and the Neoprobe Corporation (Dublin, OH, USA) for the use of a Model 2100 intraoperative radioisotope detector. Lymphoseek is a registered trademark of the Neoprobe Corporation.

References (14)

There are more references available in the full text version of this article.

Cited by (31)

  • The inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach

    2016, Nuclear Medicine and Biology
    Citation Excerpt :

    As Manocept continues to generate clinically relevant data for future applications in immunotherapies for KS (and other solid tumors), RA, TB, and cardiovascular disease, one thing remains clear: the selection of this approach, targeting CD206, appears to provide encouraging results with inter-disease consistency and reliability on the this immuno-biological strategy [43–139].

  • Status of sentinel lymph node for breast cancer

    2013, Seminars in Nuclear Medicine
    Citation Excerpt :

    It is the first radiotracer specifically designed for SLN detection. It accumulates in the lymphatic tissue by binding to mannose receptors that reside on the surface of macrophage cells.42,43 Its synthesis and biological testing was initially described in 2001 by Vera et al.44–47 Unlike the particle size–based mechanism of uptake of most technetium radiotracers used for localization of SLNs, Lymphoseek's mechanism is receptor based.

View all citing articles on Scopus
View full text