Towards Facile Radiolabeling and Preparation of Gallium-68-/Bismuth-213-DOTA-[Thi⁸, Met(O₂)¹¹]-Substance P for Future Clinical Application: First Experiences

• Main Authors: Janine Suthiram (Author), Thomas Ebenhan (Author), Biljana Marjanovic-Painter (Author), Mike M. Sathekge (Author), Jan Rijn Zeevaart (Author)
• Format: Book
• Published: MDPI AG, 2021-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics13091326; 1999-4923
• Keywords: gallium-68; ⁶⁸Ge/⁶⁸Ga generator; kit preparation; DOTA; DOTA-Substance P; [⁶⁸Ga]Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi⁸, Met(O₂)¹¹]-Substance-P; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 9, p 1326 (2021)

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi⁸, Met(O₂)¹¹]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO₂ generator matrix as well as preliminary results on the adaptability to produce [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi⁸, Met(O₂)¹¹]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP mixed with [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP. [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP providing sufficient activity for 1-2 human doses. The resultant formulation of [⁶⁸Ga]Ga-/[²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi⁸, Met(O₂)¹¹]SP-a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP and [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.