Sentinel lymph node mapping of breast cancer via intradermal administration of Lymphoseek
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)
- et al.
Minimally invasive sentinel lymph node mapping of the pig colon with Lymphoseek
Surgery
(2006) - et al.
A preclinical study of prostate sentinel node mapping with Lymphoseek
J Urol
(2006) - et al.
Dose-dependent biodistribution of [99mTc]DTPA-mannosyl-dextran for breast cancer sentinel node mapping
Nucl Med Biol
(2003) - et al.
Preclinical studies of [99mTc]DPTA-mannosyl-dextran
Nucl Med Biol
(2003) - et al.
A synthetic macromolecule for sentinel node detection: [99mTc]DTPA-mannosyl-dextran
J Nucl Med
(2001) - et al.
Sentinel lymph node mapping of the colon and stomach using Lymphoseek in a pig model
Ann Surg Oncol
(2004) - et al.
Detection of gastric and colonic sentinel nodes via endoscopic administration of Lymphoseek in pigs
J Nucl Med
(2003)
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