Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging

Early detection of bone metastases is essential to prevent skeletal-related events. Unlike biopsies, a non-invasive technique to diagnose bone metastases is by utilizing radiopharmaceuticals and detected using a nuclear imaging modality. Hence, this research deems to determine the role of gallium...

Full description

Saved in:

Bibliographic Details
Main Author:	Mohd Ashhar, Zarif Naim
Format:	Thesis
Language:	English
Published:	2020
Subjects:	Bone metastasis Radiopharmaceuticals
Online Access:	http://psasir.upm.edu.my/id/eprint/104367/1/ZARIF%20NAIM%20MOHD%20ASHHAR%20-%20IR.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-upm-ir.104367
record_format	uketd_dc
spelling	my-upm-ir.1043672023-08-08T04:10:38Z Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging 2020-06 Mohd Ashhar, Zarif Naim Early detection of bone metastases is essential to prevent skeletal-related events. Unlike biopsies, a non-invasive technique to diagnose bone metastases is by utilizing radiopharmaceuticals and detected using a nuclear imaging modality. Hence, this research deems to determine the role of gallium-68 radiolabeled bisphosphonates ([68Ga]NODAGA-Pamidronic acid) for PET bone cancer imaging. This study aims to ascertain the preparation, characterization, and radiolabeling of [68Ga]NODAGA-Pamidronic acid. Lastly, to determine its potential application, the in vitro bone binding assay and in vivo bone-to-blood ratio is examined. Firstly, NODAGA-Pamidronic acid (NODPAM) was prepared via the NHS ester conjugation method and characterized using tandem mass spectrometry (MS/MS). The RP-HPLC method was then developed to remove the free NODAGA using 0.1% trifluoroacetic acid and water as the mobile phase at a flow rate of 0.5 ml/ min. Based on the MS/MS analysis of NODPAM, the precursor ion and product ion observed were according to the theoretical value (theoretical [M-H]-m/z: 591.14, obtained [M-H]-m/z: 591.14, [M-H-H3PO3]-m/z: 509.17). The isotopic abundance M+1 (calculated m/z: 22.02, obtained m/z: 20.99±0.94) confirms the molecular formula C18H34N4O14P2. The HPLC method developed shows a good separation between peaks with a resolution of 1.613. The freeze-dried NODPAM produces a solid white powder. Next, the radiolabeling of [68Ga]NODPAM was optimized by looking into three parameters; pH, temperature, and amount NODPAM. Finally, the in vitro bone binding assay and in vivo bone-to-blood ratio was determined using synthetic hydroxyapatite and Sprague Dawley rats, respectively. From the results obtained, the %RCP of radiolabeled [68Ga]NODPAM was above 90% within 15 minutes at pH 4-4.5 and a temperature of above 60ºC. The in vitro hydroxyapatite (HA) bone binding assay displayed a significant difference between the [68Ga]NODPAM 82.25%±1.72 and [99mTc]MDP of 53.21%±0.28 (p<0.05). The bone-to-blood ratio of [68Ga]NODPAM 2-hour post-injection was significantly higher (P<0.05) compared to 68Ga(III); 27.53 and 0.74, respectively. In conclusion, [68Ga]NODPAM was prepared and characterized accordingly, and the in vitro bone binding assay and in vivo bone-to-blood ratio were assessed. The preliminary data suggests that there is a need for a complete pre-clinical study of [68Ga]NODPAM before translating it into clinical research. Bone metastasis Radiopharmaceuticals 2020-06 Thesis http://psasir.upm.edu.my/id/eprint/104367/ http://psasir.upm.edu.my/id/eprint/104367/1/ZARIF%20NAIM%20MOHD%20ASHHAR%20-%20IR.pdf text en public masters Universiti Putra Malaysia Bone metastasis Radiopharmaceuticals Yusof, Nor Azah
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
advisor	Yusof, Nor Azah
topic	Bone metastasis Radiopharmaceuticals
spellingShingle	Bone metastasis Radiopharmaceuticals Mohd Ashhar, Zarif Naim Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging
description	Early detection of bone metastases is essential to prevent skeletal-related events. Unlike biopsies, a non-invasive technique to diagnose bone metastases is by utilizing radiopharmaceuticals and detected using a nuclear imaging modality. Hence, this research deems to determine the role of gallium-68 radiolabeled bisphosphonates ([68Ga]NODAGA-Pamidronic acid) for PET bone cancer imaging. This study aims to ascertain the preparation, characterization, and radiolabeling of [68Ga]NODAGA-Pamidronic acid. Lastly, to determine its potential application, the in vitro bone binding assay and in vivo bone-to-blood ratio is examined. Firstly, NODAGA-Pamidronic acid (NODPAM) was prepared via the NHS ester conjugation method and characterized using tandem mass spectrometry (MS/MS). The RP-HPLC method was then developed to remove the free NODAGA using 0.1% trifluoroacetic acid and water as the mobile phase at a flow rate of 0.5 ml/ min. Based on the MS/MS analysis of NODPAM, the precursor ion and product ion observed were according to the theoretical value (theoretical [M-H]-m/z: 591.14, obtained [M-H]-m/z: 591.14, [M-H-H3PO3]-m/z: 509.17). The isotopic abundance M+1 (calculated m/z: 22.02, obtained m/z: 20.99±0.94) confirms the molecular formula C18H34N4O14P2. The HPLC method developed shows a good separation between peaks with a resolution of 1.613. The freeze-dried NODPAM produces a solid white powder. Next, the radiolabeling of [68Ga]NODPAM was optimized by looking into three parameters; pH, temperature, and amount NODPAM. Finally, the in vitro bone binding assay and in vivo bone-to-blood ratio was determined using synthetic hydroxyapatite and Sprague Dawley rats, respectively. From the results obtained, the %RCP of radiolabeled [68Ga]NODPAM was above 90% within 15 minutes at pH 4-4.5 and a temperature of above 60ºC. The in vitro hydroxyapatite (HA) bone binding assay displayed a significant difference between the [68Ga]NODPAM 82.25%±1.72 and [99mTc]MDP of 53.21%±0.28 (p<0.05). The bone-to-blood ratio of [68Ga]NODPAM 2-hour post-injection was significantly higher (P<0.05) compared to 68Ga(III); 27.53 and 0.74, respectively. In conclusion, [68Ga]NODPAM was prepared and characterized accordingly, and the in vitro bone binding assay and in vivo bone-to-blood ratio were assessed. The preliminary data suggests that there is a need for a complete pre-clinical study of [68Ga]NODPAM before translating it into clinical research.
format	Thesis
qualification_level	Master's degree
author	Mohd Ashhar, Zarif Naim
author_facet	Mohd Ashhar, Zarif Naim
author_sort	Mohd Ashhar, Zarif Naim
title	Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging
title_short	Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging
title_full	Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging
title_fullStr	Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging
title_full_unstemmed	Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging
title_sort	preparation and characterization of [68ga]nodaga-pamidronic acid for pet bone cancer imaging
granting_institution	Universiti Putra Malaysia
publishDate	2020
url	http://psasir.upm.edu.my/id/eprint/104367/1/ZARIF%20NAIM%20MOHD%20ASHHAR%20-%20IR.pdf
_version_	1776100432010018816

Preparation and characterization of [68Ga]NODAGA-Pamidronic acid for pet bone cancer imaging

Similar Items