Investigation of Antitumor Activity of Modified Citrus Pectin: Oral and Intravenous Administration Assessed via Molecular Imaging

This study employed molecular imaging to evaluate MCP (PectaSol-C, modified citrus pectin, a complex polysaccharide with antitumor potential) absorption and pharmacokinetics following oral and intravenous (IV) administration. MCP was radiolabeled with technetium-99m (^99mTc) ([^99mTc]MCP), allowing precise in vivo tracking. Imaging and biodistribution analyzes revealed low tumor uptake of IV [^99mTc]MCP, with predominant renal and hepatobiliary clearance. Within tumors, MCP was detected at low levels and did not bind to viable cells. Consistent with these findings, IV administration produced only modest antitumor effects (∼50% tumor growth reduction) in SKOV-3 (ovarian), MKN45 (gastric), and 4T1 (breast) grafts, whereas oral administration was ineffective due to extremely poor absorption (bioavailability <0.01%). Notably, faster clearance of [^99mTc]MCP in galectin-3 (Gal-3) knockout mice suggests a role for Gal-3 in systemic retention or an indirect contribution to antitumor activity. These findings provide new insights into MCP pharmacological profile, highlight the limitations of oral delivery, and underscore the need for improved delivery strategies to enhance the therapeutic potential of pectin-based cancer treatments.