In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites
Abstract Background Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable 67Ga-radiolabelled polymer composite that is biocompatible in an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021-03-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40824-021-00210-0 |
| _version_ | 1797282020172234752 |
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| author | Ross W. Stephens Gregory D. Tredwell Jessica L. Bell Karen J. Knox Lee A. Philip Tim J. Senden Michael J. Tapner Stephanie A. Bickley Marcel R. Tanudji Stephen K. Jones |
| author_facet | Ross W. Stephens Gregory D. Tredwell Jessica L. Bell Karen J. Knox Lee A. Philip Tim J. Senden Michael J. Tapner Stephanie A. Bickley Marcel R. Tanudji Stephen K. Jones |
| author_sort | Ross W. Stephens |
| collection | DOAJ |
| description | Abstract Background Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable 67Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs. Results Radiolabelling of polymer microspheres with 67Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent. Final in vitro binding yields after autoclaving averaged 94.7%. In vivo stability of the composite was demonstrated in New Zealand white rabbits by intravenous administration, and intrahepatic artery instillations were made in normal and VX2 tumour implanted rabbit livers. Stability of radiolabel was sufficient for rabbit lung and liver imaging over at least 3 hours and 1 hour respectively, with lung retention of radiolabel over 91%, and retention in both normal and VX2 implanted livers of over 95%. SPECT-CT imaging of anaesthetised animals and planar imaging of excised livers showed visible accumulation of radiolabel in tumours. Importantly, microsphere administration and complete liver dispersal was more easily achieved with 8 μm diameter MS than with 30 μm MS, and the smaller microspheres provided more distinct and localised tumour imaging. Conclusion This method of producing 67Ga-radiolabelled polymer microspheres is suitable for SPECT-CT imaging of the regional vascular delivery of microspheres to tumour sites in animal models. Sharper distinction of model tumours from normal liver was obtained with smaller MS, and tumour resolution may be further improved by the use of 68Ga instead of 67Ga, to enable PET imaging. |
| first_indexed | 2024-03-07T17:05:55Z |
| format | Article |
| id | doaj.art-6604bce6ff884428b4aa04740f8ffd1a |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T17:05:55Z |
| publishDate | 2021-03-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Biomaterials Research |
| spelling | doaj.art-6604bce6ff884428b4aa04740f8ffd1a2024-03-03T02:35:42ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242021-03-012511910.1186/s40824-021-00210-0In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer compositesRoss W. Stephens0Gregory D. Tredwell1Jessica L. Bell2Karen J. Knox3Lee A. Philip4Tim J. Senden5Michael J. Tapner6Stephanie A. Bickley7Marcel R. Tanudji8Stephen K. Jones9The Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National UniversityThe Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National UniversityThe Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National UniversityThe Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National UniversityThe Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National UniversityThe Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National UniversitySirtex Medical LtdSirtex Medical LtdSirtex Medical LtdSirtex Medical LtdAbstract Background Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable 67Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs. Results Radiolabelling of polymer microspheres with 67Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent. Final in vitro binding yields after autoclaving averaged 94.7%. In vivo stability of the composite was demonstrated in New Zealand white rabbits by intravenous administration, and intrahepatic artery instillations were made in normal and VX2 tumour implanted rabbit livers. Stability of radiolabel was sufficient for rabbit lung and liver imaging over at least 3 hours and 1 hour respectively, with lung retention of radiolabel over 91%, and retention in both normal and VX2 implanted livers of over 95%. SPECT-CT imaging of anaesthetised animals and planar imaging of excised livers showed visible accumulation of radiolabel in tumours. Importantly, microsphere administration and complete liver dispersal was more easily achieved with 8 μm diameter MS than with 30 μm MS, and the smaller microspheres provided more distinct and localised tumour imaging. Conclusion This method of producing 67Ga-radiolabelled polymer microspheres is suitable for SPECT-CT imaging of the regional vascular delivery of microspheres to tumour sites in animal models. Sharper distinction of model tumours from normal liver was obtained with smaller MS, and tumour resolution may be further improved by the use of 68Ga instead of 67Ga, to enable PET imaging.https://doi.org/10.1186/s40824-021-00210-0Vascular particle deliveryTumour plexusTumour imagingRadiolabelled polymer microspheresRabbit tumour model |
| spellingShingle | Ross W. Stephens Gregory D. Tredwell Jessica L. Bell Karen J. Knox Lee A. Philip Tim J. Senden Michael J. Tapner Stephanie A. Bickley Marcel R. Tanudji Stephen K. Jones In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites Biomaterials Research Vascular particle delivery Tumour plexus Tumour imaging Radiolabelled polymer microspheres Rabbit tumour model |
| title | In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites |
| title_full | In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites |
| title_fullStr | In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites |
| title_full_unstemmed | In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites |
| title_short | In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites |
| title_sort | in vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites |
| topic | Vascular particle delivery Tumour plexus Tumour imaging Radiolabelled polymer microspheres Rabbit tumour model |
| url | https://doi.org/10.1186/s40824-021-00210-0 |
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