The objective of this translational research study is to provide pilot data for the development of a targeted molecular imaging agent [Tc-99m]DTPA-mannosyl-dextran (Lymphoseek) for a new clinical application of sentinel lymph node (SLN) detection in colon cancer. The presence or absence of tumor metastases in the lymph node basin is an important prognostic feature for the staging of this cancer. In addition, the precise staging of colon cancer relies on the meticulous histopathologic detection of lymph node metastases in the surgical specimen. The SLN approach may facilitate accurate staging of patients with colon cancer by enabling the pathologist to perform a more thorough analysis of nodes likely to harbor occult metastases, using specific assays. Focused examination of the SLN with these techniques has, reportedly, upstaged colon cancer patients from AJCC Stage I/I I (node-negative) to AJCC Stage III (node-positive) disease in some series by 18 - 24% warranting adjuvant chemotherapy in this group.
The specific aims of this pilot study match the relevance of this program announcement of rapid translation of a radiopharmaceutical from the laboratory into the clinical setting which requires resource support and personnel effort.
Specific Aim 1 : Determine the radiation absorbed dose of the injection site at the primary colon cancer and the feasibility of intraoperative lymph node mapping using a 2 nmol injected molar dose measured with a calibrated intraoperative gamma probe and gamma well counter.
Specific Aim 2 : Document the safety of the agent by patient monitoring of clinical laboratory tests. Our long-term goal is to use the proven biologic properties of Lymphoseek to remove a barrier to SLN mapping of Gl cancers. Currently only blue dye or filtered Tc-99m-Sulfur Colloid have been used for SLN mapping of colorectal cancer. Most surgeons find both very difficult to use in the Gl tract and, consequently have not accepted the technique for colorectal cancer. If this pilot study is successful, then this new agent can be tested in Phase II and III clinical studies with the objective of more accurately staging colon cancer. From the public health perspective, this may allow colon cancer patients to be enrolled into adjuvant therapy protocol (if their sentinel node is positive) or to know that they are in a potentially new clinical stage category with very low likelihood of disease recurrence (if their sentinel node is negative). ? ? ?
