Replacing 99mTc with 111In improves MORF/cMORF pretargeting by reducing intestinal accumulation

Objectives When labeled with ^99mTc and used for MORF/cMORF pretargeting of tumors, the cMORF effector was found to accumulate in the intestines in mice at levels that would interfere with detection of tumor or other tissues by imaging in the abdomen. To minimize this accumulation, ¹¹¹In was compared to ^99mTc as the cMORF radiolabel.

Methods Two normal mice received IV either ^99mTc- or ¹¹¹In-cMORF and were repeatedly imaged for pharmacokinetics over 1 h on a small animal multipinhole SPECT/CT camera. Additional normal animals receiving these injectates were sacrificed at 15 min for biodistribution by necropsy. Finally, two nude mice bearing LS174T tumors in a thigh received the MORF-CC49 antibody 2 days prior to receiving either the ^99mTc- or ¹¹¹In-cMORF and were imaged at different times thereafter.

Results By both imaging and necropsy, renal excretion in normal mice was the major route of whole body clearance for both ^99mTc and ¹¹¹In-cMORF. Tissues other than kidneys, gallbladder, and intestines were essentially free of either ^99mTc or ¹¹¹In-cMORF. By necropsy, about 2 % of ^99mTc accumulated in the intestines in the first 15 min following IV administration compared to essentially no intestinal accumulation for ¹¹¹In at any time. Imaging results in tumored mice confirmed the considerably higher intestinal and hepatobilliary accumulation of ^99mTc compared to ¹¹¹In. Tumor accumulations were identical.

Conclusions In applications of MORF/cMORF pretargeting intended to image tumor or organs deep within the abdomen such as the diabetic pancreas, radiolabeling with ¹¹¹In may be superior to ^99mTc.