In vivo evaluation of an 111In-labeled ST-peptide analog for specific-targeting of human colon cancers

Area of Science:

• Radiopharmaceutical chemistry
• Molecular imaging
• Oncology

Background:

• Guanylate cyclase-C (GC-C) receptors are overexpressed in certain gastrointestinal cancers, making them a target for diagnostic and therapeutic agents.
• Developing targeted radiopharmaceuticals requires peptides with high affinity and specificity for cancer biomarkers.

Purpose of the Study:

• To evaluate the in vitro and in vivo performance of an Indium-111 (111In)-labeled DOTA-ST peptide analog for targeting GC-C receptors on human colon cancer cells.
• To assess the potential of this radiolabeled peptide as a diagnostic and therapeutic radiopharmaceutical.

Main Methods:

• In vitro competitive binding assays using LS-180 colon cancer cells to determine IC50 values.
• In vitro cellular residualization studies to assess receptor-mediated uptake and function.
• In vivo biodistribution studies in SCID mice bearing LS-180 tumors to evaluate tumor targeting and clearance pathways.

Main Results:

• The 111In-DOTA-NCS-ST peptide showed high binding affinity to GC-C receptors with an IC50 of 7.7 nM.
• In vitro studies confirmed selective binding and agonistic activity in LS-180 cells.
• In vivo studies demonstrated specific tumor targeting (0.94%ID/g at 1 hr) and retention (23% at 4 hrs) in LS-180 tumors.
• Rapid clearance from blood via the renal/urinary pathway was observed, with minimal uptake in liver and intestines.

Conclusions:

• The 111In-DOTA-NCS-ST peptide demonstrates selective in vitro and in vivo accumulation in human colonic cancer cells.
• These findings highlight the potential of radiometallated DOTA-ST analogs as effective diagnostic and therapeutic radiopharmaceuticals for colon cancer.