Journal article
Radiolabeling optimization and characterization of 68Ga labeled DOTA–polyamido-amine dendrimer conjugate – Animal biodistribution and PET imaging results
Applied radiation and isotopes, Vol.105, pp.40-46
11/2015
DOI: 10.1016/j.apradiso.2015.07.021
PMCID: PMC5538890
PMID: 26232562
Abstract
The present study describes the optimization of 68Ga radiolabeling with PAMAM dendrimer–DOTA conjugate. A conjugate (PAMAM–DOTA) concentration of 11.69µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0min and reaction temperature ranging between 90 and 100°C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([68Ga]-DOTA–PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good ‘non-specific’ tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA–PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the 68Ga labeled product for imaging and treating angiogenesis respectively.
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•Chemical conjugation of G-4 PAMAM dendrimers with DOTA-NHS carried out successfully.•Purification and characterization of the conjugate was done by SEC and MALDI-TOF.•Radiolabeling of PAMAM-DOTA-conjugate with 68Ga yielded high radiolabeling efficiency.•[68Ga] DOTA–PAMAM-Dhas rapid blood clearance and excreted mainly through the kidneys.•No significant retention of the radiotracer was seen in any other organ.
Details
- Title: Subtitle
- Radiolabeling optimization and characterization of 68Ga labeled DOTA–polyamido-amine dendrimer conjugate – Animal biodistribution and PET imaging results
- Creators
- Aanchal Ghai - Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, IndiaBaljinder Singh - Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, IndiaPuja Panwar Hazari - Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, IndiaMichael K Schultz - Department of Radiation Oncology, Free Radical and Radiation Biology Program, The University of Iowa, 500 N Road, ML B180 FRRB, Iowa City, IA, USAAmbika Parmar - Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, IndiaPardeep Kumar - Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, IndiaSarika Sharma - Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, IndiaDevinder Dhawan - Centre for Nuclear Medicine, Punjab University, Chandigarh 160 014, IndiaAnil Kumar Mishra - Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, India
- Resource Type
- Journal article
- Publication Details
- Applied radiation and isotopes, Vol.105, pp.40-46
- DOI
- 10.1016/j.apradiso.2015.07.021
- PMID
- 26232562
- PMCID
- PMC5538890
- NLM abbreviation
- Appl Radiat Isot
- ISSN
- 0969-8043
- eISSN
- 1872-9800
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/501100001411, name: Indian Council of Medical Research
- Language
- English
- Date published
- 11/2015
- Academic Unit
- Radiology; Stead Family Department of Pediatrics; Radiation Oncology
- Record Identifier
- 9984216677102771
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