This is a two part, open-label, non-randomized trial that will be conducted at Thomas Jefferson University (TJU). Initially in Part 1, a two-period, crossover, dose-finding study will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. Each volunteer will receive an injection of a low or a high dose in a blinded, sequence-randomized allocation schedule. Screening and baseline assessments/procedures will be obtained. Each volunteer will receive their subdermal, low or high dose of Sonazoid divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock) around a 2 cm in diameter region in the mid-upper outer quadrant of the left breast.~Contrast enhanced ultrasound imaging (CEUS) will be performed immediately after Sonazoid administration (i.e., lymphosonography) to identify the number, location and course of the lymphatic channels (LCs) and SLNs using a S3000 scanner (Siemens Medical Solutions, Mountain View, CA) with a high frequency, broad bandwidth linear array. CEUS evaluations will be repeated at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours and 24 hours post Sonazoid administration. The safety and tolerability of Sonazoid will be closely monitored throughout this safety and tolerability, dose-finding study.~Following at least a one week of washout, the upper outer quadrant of the right breast will be injected with the alternate dose of Sonazoid and lymphosonography will again be used to identify the number, location and course of the LCs and SLNs. Volunteers who received the low dose during their first visit will receive the high dose the next time around and vice versa in a 1:1 ratio. All procedures from the initial visit will be repeated (see above), except that the left breast (injected initially) will be assessed sonographically for the presence of contrast-enhanced tissues (injection site as well as lymphatic structures) prior to contrast administration in the right breast.~In Part 2 lymphosonography will compare SLN identification to that of isotope mapping during surgery on 90 female, breast cancer patients. A state-of-the-art S3000 scanner with contrast-specific imaging capabilities will be used to localize lymphatic drainage from breast cancers after subdermal administration of Sonazoid. The number and locations of the SLNs identified by the two imaging modalities (CEUS and isotope mapping) will be compared with dye-guided surgery as the reference standard for SLN detection. Moreover, as each SLN is resected it will be assessed ex vivo for the presence of radioactivity (using a gamma probe), Sonazoid (using CEUS) and blue dye (via visual inspection by the surgeon). All SLNs that are surgically removed will be documented and sent for histopathologic evaluation.~Trial Population: Part 1 will consist of 12 healthy, adult female volunteers in the initial safety, tolerability and dosing study.~In Part 2, 90 adult women, who have breast cancer and are scheduled for a surgical excision and SLN evaluation, will be enrolled in a clinical trial at TJU.~Statistical Methodology: Our statistical analysis will address four major questions:~Is subdermal administration of Sonazoid in humans safe and tolerable?~Can an optimal and efficacious dose of Sonazoid for lymphosonography be established?~Does lymphosonography identify more SLNs in patients with breast cancer than isotope mapping (with Tc-99m sulfur colloids)?~Does lymphosonography identify more SLNs with metastatic deposits in patients with breast cancer compared to isotope mapping?
This is a two part, open label, non-randomized trial of women with a breast cancer diagnosis scheduled for excisional surgery and sentinel lymph node (SLN) evaluation.~Part 1 is a two-period, crossover, dose-finding study, which will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. In Part 2 lymphosonographic SLN identification will be compared to that of isotope mapping during surgery on 90 female, breast cancer patients.