CD206-targeted Cy3-Manocept (Mano-Cy3) localizes in nearly all cells present in Kaposi’s sarcoma representing an opportunity for dynamic imaging, local staging and a potential for visceral metastasis imaging

Objectives In patients with Kaposi’s sarcoma (KS), plasma elevation of macrophage (MP)-produced growth factors such as EGF and bFGF suggests a role for tumor associated MPs (TAMs) in KS pathogenesis. The goals of the current study were two-fold: 1) to define MP subsets using M1 (MAC387), M2 (CD163, CD206) and pan MP (CD68) antibodies (Ab) in tissue microarray (TMA) analysis of KS including plaque, oral and visceral tumors; 2) To test whether CD206, the MP mannose receptor (MMR) recognized by CD206-targeted Mano-Cy3, is present on TAMs and KS tumor cells. If TAMs and KS cells are CD206+, Manocept could allow for dynamic imaging, local staging and a potential for visceral metastasis imaging of KS.

Methods A KS TMA with 66 KS cases and controls was obtained from the AIDS and Cancer Specimen Resource (ACSR). MPs were identified by IHC studies and results were standardized to the proportion of KSHV LANA+ cells (KS specific marker). ACSR KS specimens from Africa were also tested.

Results TAMs in KS were identified with the M2 anti-CD163 Ab and the M1 anti-MAC387 Ab. The pan-MP-CD68 Ab also identified TAMs in >90% of tumors. KS tumor spindle cells expressed MP antigens; however the most prevalent antigen for both KS tumor spindle cells (LANA+) and TAMs was the MMR (CD206). Expression of MP antigens and Mano-Cy3:CD206 in relation to level of LANA within tumor tissues was similar across all tissue forms of KS (plaque, oral, visceral).

Conclusions This study confirmed TAMs and KS tumor cells express CD206. A radio-ligand form of Mano-Cy3, Tc99m-Manocept may allow effective imaging of KS involved nodes and visceral sites of disease. The potential for using Tc99m-Manocept to define tumor burden may allow early tumor specific treatment beyond the current use of anti-retroviral therapy which is proving ineffective in growing numbers of KS patients.