journal article·2021-02-12Open access

In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites

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

Biomaterials Research· Volume 25· Issue 1

Abstract

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 67 Ga-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 67 Ga 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 67 Ga-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 68 Ga instead of 67 Ga, to enable PET imaging.
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Research context

OpenAlex topics: Tissue Engineering and Regenerative Medicine · Nanoplatforms for cancer theranostics · Peptidase Inhibition and Analysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National University, Canberra, ACT, Australia.

Sirtex Medical Ltd, Sydney, Australia.

References (22)

Show source-provided references
1. 10.1111/j.1445-2197.1992.tb00006.x10.1111/j.1445-2197.1992.tb00006.x ↗
2. 10.1186/1477-7819-9-8610.1186/1477-7819-9-86 ↗
3. 10.1016/0277-5379(89)90109-010.1016/0277-5379(89)90109-0 ↗
4. 10.2147/IJN.S18715310.2147/IJN.S187153 ↗
5. Johnston GS, Go MF, Benua RS, Larson SM, Andrews GA, Hubner KF. Gallium-67 citrate imaging in Hodgkin's disease: final report of cooperative group. J Nucl Med. 1977;18(7):692–698. 1:STN:280:DyaE2s3gslOgug%3D%3D
6. Ehrhardt GJ, Welch MJ. A new germanium-68/Gallium-68 generator. J Nucl Med. 1978;19(8):925–929. 1:CAS:528:DyaE1cXlsFCgtrc%3D
7. 10.1016/0020-708X(81)90132-010.1016/0020-708X(81)90132-0 ↗
8. 10.1016/0883-2889(88)90091-310.1016/0883-2889(88)90091-3 ↗
9. Iffat AT, Maqsood ZT, Fatıma N. Study of complex formation of Fe (III) with tannic acid. J Chem Soc Pak. 2005;27:174–177. 1:CAS:528:DC%2BD2MXhtV2gs73E
10. 10.3390/ijms1012548510.3390/ijms10125485 ↗
11. 10.1146/annurev.nu.10.070190.00102510.1146/annurev.nu.10.070190.001025 ↗
12. Brown SJ, Slizofski WJ, Dadparvar S. Altered biodistribution of Gallium-67 in a patient with aluminum toxicity treated with desferoxamine. J Nucl Med. 1990;31(1):115–117. 1:STN:280:DyaK3c7htFymtw%3D%3D
13. 10.1039/p2991000008710.1039/p29910000087 ↗
14. 10.1002/chem.20110350310.1002/chem.201103503 ↗
15. 10.1088/0031-9155/46/12/30710.1088/0031-9155/46/12/307 ↗
16. 10.1016/j.ultrasmedbio.2015.02.01210.1016/j.ultrasmedbio.2015.02.012 ↗
17. 10.2217/fon-2018-019610.2217/fon-2018-0196 ↗
18. 10.3109/1073968970914831510.3109/10739689709148315 ↗
19. 10.1016/j.bbrc.2019.03.06610.1016/j.bbrc.2019.03.066 ↗
20. Stephens RW, Bell JL. Radiolabelled material. 2019. USA Patent 10,232,062.
21. 10.1002/jso.111810.1002/jso.1118 ↗
22. 10.1016/j.jvir.2008.09.03310.1016/j.jvir.2008.09.033 ↗