Endocrine Abstracts

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 5 months on radiolabeling DOTATATE, PSMA^HEBD/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 0.05 mg DOTATATE and 0.005 mg PSMA^HEBD-CC; ²¹³Bi was quantitatively complexed using 0.1 mg 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-PSMA^HEBD-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 0.05 mg, 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 0.05 mg, 222–259 MBq, n=3) after 5, 10 and 15 min incubation, respectively.

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

References

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.