Introduction: Targeted pharmaceuticals for labelling with radio-isotopes for very specific
imaging (and possibly later for targeted therapy) play a major role in Theranostics which is
currently an important topic in Nuclear Medicine as well as personalised medicine. There
was a need for a very specific lung cancer radiopharmaceutical that would specifically be
uptaken in integrin 3 expression cells to image patients using a Positron Emission
Tomography- Computed Tomography (PET-CT) scanner.
Background and problem statement: Cold kits of c (RGDyK)–SCN-Bz-NOTA were kindly
donated by Seoul National University (SNU) to help meet Steve Biko Hospital’s need for
this type of imaging. These cold kits showed great results internationally in labelling with a
0.1 M 68Ge/68Ga generator (t1/2 of 68Ge and 68Ga are 270.8 days and 67.6 min,
respectively). However the same cold kits failed to show reproducible radiolabeling with the
0.6 M generator manufactured under cGMP conditions at iThemba LABS, Cape Town and
distributed by IDB Holland, the Netherlands.
Materials and methods: There was therefore a need for producing an in-house NOTA-RGD
kit that would enable production of clinical 68Ga-NOTA-RGD in high yields from the IDB
Holland/iThemba LABS generator. Quality control included ITLC in citric acid to observe
labelling efficiency as well as in sodium carbonate to evaluate colloid formation. HPLC was
also performed at iThemba LABS as well as Necsa (South African Nuclear Energy
Corporation). RGD was obtained from Futurechem, Korea. Kit mass integrity was
determined by testing labelling efficiency of 10, 30 and 60 μg of RGD per cold kit. The
RGD was buffered with sodium acetate trihydrate. The original kits were dried in a
desiccator and in later studies only freeze dried. Manual labelling was also tested. The
radiolabelled in-house kit’s ex vivo biodistribution in healthy versus tumour mice were
examined by obtaining xenografts. The normal biodistribution was investigated in three
vervet monkeys by doing PET-CT scans on a Siemens Biograph TP 40 slice scanner.
Results: Cold kit formulation radiolabeling and purification methods were established
successfully and SOPs (standard operating procedures) created. HPLC results showed
highest radiochemical purity in 60 μg cold kit vials. 68Ga-NOTA-RGD showed increased
uptake in tumours of tumour bearing mouse. The cold kit also showed normal distribution
according to literature with fast blood clearance and excretion through kidneys into urine,
therefore making it a suitable radiopharmaceutical for clinical studies.
Conclusion: The in-house prepared cold kit with a 4 month shelf-life was successfully
tested in mice and monkeys. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/13428 |
| Date | January 2014 |
| Creators | Schoeman, Isabel |
| Source Sets | North-West University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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