東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Panitumumab Modified with Metal Chel...

Aghevlian, Sadaf.

Linked to FindBook

Google Book

Amazon

博客來

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

Record Type:	Electronic resources : Monograph/item
Title/Author:	Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer./
Author:	Aghevlian, Sadaf.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	229 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Contained By:	Dissertations Abstracts International81-06B.
Subject:	Oncology. -
Online resource:	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.
LDR:03588nmm a2200373 4500 001 2272462
005 20201105110100.5
008 220629s2019 ||||||||||||||||| ||eng d
020 $a 9781392477458
035 $a (MiAaPQ)AAI13857820
035 $a AAI13857820
040 $a MiAaPQ $c MiAaPQ
100 1 $a Aghevlian, Sadaf. $3 3549900
245 1 0 $a Panitumumab Modified with Metal Chelating Polymers (MCPs) Complexing Indium‐111 and Lutetium-177 as Theranostics for Pancreatic Cancer.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 229 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
500 $a Advisor: Reilly, Raymond M.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2019.
506 $a This item must not be sold to any third party vendors.
520 $a 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.
590 $a School code: 0779.
650 4 $a Oncology. $3 751006
650 4 $a Pharmaceutical sciences. $3 3173021
653 $a 111In
653 $a 177Lu
653 $a EGFR
653 $a Pancreatic cancer
653 $a Radioimmunoterapy
653 $a Theranostics
690 $a 0992
690 $a 0572
710 2 $a University of Toronto (Canada). $b Pharmaceutical Sciences. $3 3170825
773 0 $t Dissertations Abstracts International $g 81-06B.
790 $a 0779
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13857820