![]() ![]() Pancreatic cancer (PnCa) is one of the most lethal cancers since most patients are diagnosed when there is local invasion or metastasis, rendering these patients ineligible for surgical treatment (Kamisawa et al., 2016). We conclude that EGFR-targeted RIT is a promising approach to treatment of PnCa. PANC-1 tumours in NOD/SCID or NRG mice, at administered amounts that caused no normal tissue toxicity. RIT with panitumumab labeled with Auger electron-emitting, 111In or β-particle-emitting, 177Lu inhibited the growth of s.c. The absorbed doses in PANC-1 tumours were 8.8 ± 3.0 Gy and 2.6 ± 0.3 Gy for panitumumab-DOTA-In and panitumumab-MCP-In, respectively, and 11.6 ± 4.9 Gy for panitumumab-DOTA-Lu. 11.5 days for panitumumab and 9.1 days for normal saline. PANC-1 tumours with 6.0 MBq (10 μg ~ 0.07 nmoles) of panitumumab-DOTA-Lu increased the TDT to 20.9 days vs. 15.6 days for normal saline treated mice. Panitumumab was ineffective yielding a TDT of 15.3 days vs. PANC-1 tumours treated with panitumumab-DOTA-In or panitumumab-MCP-In was 51.8 days and 28.1 days, respectively. The tumour doubling time (TDT) for NOD/SCID mice with s.c. RIT inhibited the growth of PANC-1 tumours but a 5-fold greater total amount of panitumumab-DOTA-In or panitumumab-MCP-In (30 MBq 30 μg ~ 0.21 nmoles) administered in three fractionated amounts every three weeks was required to achieve greater or equivalent tumour growth inhibition, respectively, compared to a single amount of panitumumab-DOTA-Lu (6 MBq 10 μg ~ 0.07 nmoles). There was no decrease in complete blood cell counts (CBC) or increased serum alanine aminotransferase (ALT) or creatinine (Cr) or decreased body weight. No normal tissue toxicity was observed in NOD/SCID mice injected intravenously (i.v.) with 10.0 MBq (10 μg ~ 0.07 nmoles) of panitumumab-DOTA-In or panitumumab-MCP-In or in NRG mice injected i.v. The absorbed dose in the nucleus was 3.9-fold higher for panitumumab-DOTA-Lu than panitumumab-DOTA-In and 7.7-fold greater than panitumumab-MCP-In. ![]() Panitumumab-DOTA-Lu caused the greatest density of DNA double-strand breaks (DSBs) in the nucleus measured by immunofluorescence for γ-H2AX. Panitumumab-DOTA-Lu was more effective per MBq exposure at reducing the clonogenic survival in vitro of PANC-1 cells than panitumumab-DOTA-In or panitumumab-MCP-In. Panitumumab was conjugated to DOTA chelators for complexing 111In or 177Lu (panitumumab-DOTA-In and panitumumab-DOTA-Lu) or to a metal-chelating polymer (MCP) with multiple DOTA to bind 111In (panitumumab-MCP-In). Our aim was to study RIT of subcutaneous (s.c.) PANC-1 human PnCa xenografts in mice using the anti-EGFR monoclonal antibody, panitumumab labeled with Auger electron (AE)-emitting, 111In or β-particle emitting, 177Lu at amounts that were non-toxic to normal tissues. Epidermal growth factor receptors (EGFR) are overexpressed on > 90% of pancreatic cancers (PnCa) and represent an attractive target for the development of novel therapies, including radioimmunotherapy (RIT). ![]()
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