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Panitumumab Modified with Metal Chel...

Aghevlian, Sadaf.

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Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer./
作者:	Aghevlian, Sadaf.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	229 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Contained By:	Dissertations Abstracts International81-06B.
標題:	Oncology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13857820
ISBN:	9781392477458

Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer.
Aghevlian, Sadaf.

Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 229 p.

Source: Dissertations Abstracts International, Volume: 81-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

The epidermal growth factor receptor (EGFR) is overexpressed in more than 90% of pancreatic cancer (PnCa) patients. A metal-chelating polymer (MCP) with on average 13 DOTA (tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators for complexing the β-particle emitter, 177Lu and Auger electron-emitter, 111In and 10 polyethylene glycol (PEG) chains was conjugated to monoclonal antibody, panitumumab to target EGFR on PANC-1 human PnCa cells. Linking panitumumab to MCPs enabled dual labeling with 111In and 177Lu at a higher SA (55.9± 4.8 MBq/μg and 20.5± 4.2 MBq/μg) compared to panitumumab-DOTA (4.4± 0.3 MBq/μg and 2.2± 0.3 MBq/μg), with preserved EGFR binding (2.2 ± 0.6 nmol/L and 1.0 ± 0.4 nmol/L; respectively) and comparable tumour (6.9 ± 1.3% ID/g and 6.6 ± 3.3%ID/g) and normal tissue localization except for the liver uptake which was 3-fold higher for panitumumab-MCP at 72 h post injection (p.i.) in NOD/SCID mice with s.c. PANC-1 xenografts as confirmed by microSPECT/CT imaging. 177Lu-labeled radioimmunoconjugates (RICs) were more effective for killing PANC-1 cells in vitro than 111In-RICs with no significant differences between panitumumab-DOTA and panitumumab-MCP. For therapy, NOD/SCID mice or NRG mice with s.c. PANC-1 tumors were administered three amounts (10 MBq; 10 g) of panitumumab-MCP-111In or panitumumab-DOTA-111In separated by 3 weeks or a single amount (6 MBq; 10 g) of panitumumab-MCP-177Lu or panitumumab-DOTA-177Lu, respectively. Tumour growth was assessed by a tumour growth index (TGI). Panitumumab-MCP-111In or panitumumab-DOTA-111In inhibited tumour growth in NOD/SCID mice (TGI at 43 days = 3.9 ± 0.3 and 3.0 ± 0.4, respectively; P> 0.05) compared to normal saline and panitumumab treated mice (TGI = 9.8 ± 1.6, 9.9 ± 1.4, respectively; P>0.5). Similarly, panitumumab-MCP-177Lu and panitumumab-DOTA-177Lu inhibited tumour growth in NRG mice (TGI at 33 days = 2.5 ± 0.3 and 1.8± 0.3; respectively; P> 0.05) compared to normal saline and panitumumab treated mice (5.8 ± 0.9 vs. 6.1 ± 2.7, respectively; P>0.05). 177Lu-RICs deposited more absorbed doses in tumours (2-4 fold) and normal organs compared to 111In-RICs. Low absorbed doses in the normal organs for 111In allow for dose escalation. Panitumumab conjugates labeled with 177Lu or 111In are promising RIT agents for treatment of EGFR positive cancers.

ISBN: 9781392477458Subjects--Topical Terms:

751006
Oncology.
Subjects--Index Terms:

111In

Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer.
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