Initial South African experience on <sup>68</sup>Ga/<sup>213</sup>Bi radiolabeling for prospective theranostics — ASN Events
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  3. Initial South African experience on 68Ga/213Bi radiolabeling for prospective theranostics

Initial South African experience on 68Ga/213Bi radiolabeling for prospective theranostics (#44)

Thomas Ebenhan 1 , Janine Suthiram 1 2 , Danka Erasmus 1 , Otto Knoesen 3 , Judith Wagener 2 , Biljana Marjanovic-Painter 2 , Jan Rijn Zeevaart 2 4 , Sebastian Marx 5 , Marian Meckel 5 , Mike M Sathekge 1
  1. Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Gezina/Pretoria, Gauteng, South Africa
  2. Radiochemistry, The South African Nuclear Energy Corporation (Necsa), Brits Magisterial District, Madibeng Municipality, North West Province, South Africa
  3. Technology Department, NTP Radioisotopes SOC Ltd, Pretoria, Gauteng, South Africa
  4. Preclinical Drug Development Platform, Department of Science and Technology, North West University, Potchefstroom, North West Province, South Africa
  5. ITG Isotope Technologies Garching GmbH, Lichtenbergstrasse 1 , 85748 Garching, Germany

Background The current focus of personalized medicine is towards the use of the theranostic approach - the development of an interdependent, collaborative targeted therapeutic and a companion diagnostic test. [DOTA0,D-Phe1,Tyr3]-octreotate (DOTA-TATE) and ligands targeting prostate-specific membrane antigen (PSMA) have been introduced recently as 177Lu-labeled theranostics for neuroendocrine tumors and prostate cancer respectively [1, 2]. DOTA-RP001 is a novel 11-mer peptide conjugate, envisaged as a theranostic agent against pancreatic cancer. For this study, 213Bi which can be complexed by the DOTA-functionalized compounds for alpha-emitting radionuclide therapy is supported by 68Ga, a PET-isotope prioritized for diagnostic imaging. 213Bi was initially introduced clinically for radioimmunotherapy [3]. We report initial empirical values gained over the past five months on radiolabeling DOTATATE, PSMAHEBD/DOTA-PSMA-617 and DOTA-RP001 with 68Ga and 213Bi, pioneering this procedure in South Africa.

Methods 68Ga and 213Bi were obtained by eluate fractionation from 68Ga/68Ge-generators (iThembaLABS, Somerset West, South Africa) and 225Ac/213Bi-generators (ITG, Garching, DE); sodium acetate buffered bioconjugates (pH 3.5-5) were incubated at 93-95 °C for 15 min followed by purification. Final solutions were sterilized by filtration directly to syringes diluted to ~10 ml. Radiochemical purity and yields were assessed by HPLC/ITLC-SG.

Results 68Ga-labeling succeeded using 0.05mg DOTATATE and 0.005mg PSMAHEBD-CC; 213Bi was quantitatively complexed using 0.1mg DOTATATE or DOTA-PSMA-617. All patient administrations were successful. 68Ga-DOTATATE-PET/CT was carried out (133-259 MBq, n=15) to support 213Bi-DOTATATE treatment (259-370 MBq). 68Ga-PSMAHEBD-CC-PET/CT (120-240 MBq, n>20) was performed to facilitate 213Bi-DOTA-PSMA-617 treatment (222-407 MBq). The method translated well to yield 77±20% (decay-corrected) 68Ga-DOTA-RP001 (using 0.05mg, RCP ≥96.4% after purification, 162-336 MBq, n=5) and a RCP of 65.7%, 91.2% and 97.5% for 213Bi-DOTA-RP001 (using 0.05mg, 222-259 MBq, n=3) after 5, 10 and 15 minutes incubation, respectively.

Conclusion The data indicates that a robust preparation and safe administration to humans warrants prospective clinical studies with 68Ga/213Bi-theranostic agents.

  1. Baum, R.P., Kulkarni, H.R., Theranostics. 2012; 2:437-47
  2. Weineisen, M., et al., J Nucl Med. 2015; 56:1169-76
  3. Song, H., et al., Cancer Res. 2009; 69:8941-8