¹¹¹In-labeled immunoliposomes targeting both epithelioid and sarcomatoid mesothelioma

Objectives The objectives of the study was to evaluate the in vitro and in vivo tumor targeting of novel human ScFv (M1) anchored immunoliposmes (ILs) on both epithelioid(M-28) and sarcomatoid (VAMT-1) mesothelioma.

Methods Immunoliposomes (ILs) were prepared by a thin-film extrusion method followed by insertion of M1 & radiolabeled with ¹¹¹In via DTPA conjugated to the liposome (¹¹¹In-IL). For in vitro cell studies, ¹¹¹In-IL was incubated at 37^oC for 24h with M-28, VAMT-1 & a control cell-line (BPH). For animal studies, the ¹¹¹In-IL or control liposome was injected i.v. to athymic mice bearing M-28 & VAMT-1 tumors on the right & left shoulders respectively. Mice were imaged with μ-SPECT/CT at 24h & 48h, & sacrificed at 24h or 48h post-injection to assess biodistribution.

Results The labeling efficiency of the IL was >95% after purification. ¹¹¹In-IL was stable during the time course of study. ¹¹¹In-IL efficiently internalized into both subtypes of mesothelioma tumor cells but not in the non-target BPH cells; 81-94% of the total cell accumulation at 37^oC accounted to internalization at 24h incubation for the mesothelioma cells whereas only 37-55% of the total was accounted for internalization in control (BPH) cell line. In animal studies, at 24h the accumulation of ¹¹¹In-IL in mesothelioma tumors was next only to liver and spleen while the tumor uptake at 48h was next only to liver. The tumor uptake was 4.7 %ID/g & 4%ID/g for VAMT-1 & M-28 tumors respectively at 48h. In contrast, at 48h the control liposome exhibited tumor uptake of only 0.5%ID/g & 0.6 %ID/g for VAMT-1 & M-28 tumors respectively.

Conclusions The M1 immunoliposomes showed selective tumor targeting to both epithelioid (M-28) & sarcomatoid (VAMT-1) human mesothelioma cancer cells, demonstrating its potentials as a promising vector for radioimmunotherapy, when labeled with therapeutic radionuclides.

Research Support NIH/NCI R01CA 135358-01, IRG-97-150-10/ACS