RT Journal Article
SR Electronic
T1 A novel rapidly internalizing human single chain antibody fragment targeting both epithelioid and sarcomatoid mesothelioma
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 395
OP 395
VO 51
IS supplement 2
A1 Iyer, Arun
A1 Lan, Xiaoli
A1 Zhu, Xiaodong
A1 Feng, Jinjin
A1 Su, Yang
A1 Zhang, Xiaoju
A1 Seo, Youngho
A1 VanBrocklin, Henry
A1 Liu, Bin
A1 He, Jiang
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/395.abstract
AB 395 Objectives The objectives of this study was to evaluate the in vitro cell internalization & in vivo tumor targeting of a novel internalizing human ScFv (M40) on both epithelioid (M-28) & sarcomatoid (VAMT-1) subtypes of mesothelioma. Methods The M40 was engineered to contain a hexahistidine tag to accommodate 99mTc-tricarbonyl labeling (99mTc-M40). For in vitro cell studies, 99mTc-M40 was incubated at 37oC for 1&3h with M-28 & VAMT-1 mesothelioma cells & a control cell-line (BPH). For animal studies, 99mTc-M40 was injected i.v. to athymic mice implanted s.c. with both M-28 and VAMT-1 tumors on the right & left shoulders respectively. A blocking control study with excess unlabeled M40 followed by 99mTc-M40 was performed. For comparative studies mice bearing both tumors were imaged with μ-SPECT/CT for 99mTc-M40 or μ-PET/CT for 18F-FDG & sacrificed at 1, 3 or 6h to assess biodistribution. Results The 99mTc-M40 rapidly internalized into both subtypes of tumor cells but not in non-targeted cells & 81-91% of total cell accumulation was accounted for internalization at 37oC, as early as within 1h. In animal studies, the 99mTc-M40 was rapidly eliminated from blood & most normal organs (except kidneys), giving tumor uptake >5.84 %ID/g & 4.38 %ID/g for VAMT-1 & M-28 tumors respectively at 3h. In contrast, the control blocking study at 3h exhibited tumor uptake ≤1.6%ID/g & 0.9 %ID/g for VAMT-1 & M-28 tumors respectively. More importantly, in mice bearing both tumors, SPECT/CT using 99mTc-M40 could image both epitheliod & sarcomatoid mesothelioma whereas the PET/CT using 18F-FDG could image only sarcomatoid mesothelioma. Conclusions The 99mTc-M40 showed rapid internalization & selective tumor targeting in both epithelioid (M-28) & sarcomatoid (VAMT-1) human mesothelioma cancer cells, demonstrating potential use in targeted imaging and therapy. Research Support NIH/NCI R01CA 135358-01 & IRG-97-150-10/ACS