Intricacies in the Preparation of Patient Doses of [177Lu]Lu-Rituximab and [177Lu]Lu-Trastuzumab Using Low Specific Activity [177Lu]LuCl3: Methodological Aspects

• Published in: Molecular imaging and biology Vol. 26; no. 1; pp. 61 - 80
• Main Authors: Chakraborty, Avik, Mitra, Arpit, Sahu, Sudeep, Tawate, Megha, Lad, Sangita, Kamaldeep, Rakshit, Sutapa, Upadhye Bannore, Trupti, Gaikwad, Sujay, Dhotre, Geetanjali, Ray, Mukti Kanta, Damle, Archana, Basu, Sandip, Banerjee, Sharmila
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-02-2024; Springer Nature B.V
• Subjects: Ascorbic acid; Breast cancer; Breast carcinoma; Conjugation; Imaging; Immunoconjugates; Localization; Lutetium; Lutetium isotopes; Lymphoma; Medicine; Medicine & Public Health; Metastases; Monoclonal antibodies; Patients; Radiochemistry; Radiolabelling; Radiology; Research Article; Rituximab; Trastuzumab; Clinical and pre-clinical study; Radioimmunotherapy; Rituximab; Breast cancer; Lu-177; Lymphoma; Trastuzumab
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-023-01846-1

The development of humanized monoclonal antibodies (MAbs) with Lutetium-177 ([
177
Lu]Lu
3+
) has brought a paradigm shift in the arena of targeted therapy of various cancers. [
177
Lu]Lu-DOTA-Rituximab and [
177
Lu]Lu-DOTA-Trastuzumab have gained prominence due to their improved therapeutic efficacy in the treatment of lymphoma and breast cancer. The clinical dose formulation of these radiolabeled MAbs, using low specific activity [
177
Lu]LuCl
3
, requires extensive optimization of the radiolabeling protocol. The present study merits the development of a single protocol which has been optimized for conjugation of Rituximab and Trastuzumab with
p
-NCS-benzyl-DOTA and further radiolabeling these immunoconjugates (ICs) with low specific activity [
177
Lu]LuCl
3
. Herein, we report a consistent and reproducible protocol for clinical dose formulations of [
177
Lu]Lu-DOTA-Rituximab and [
177
Lu]Lu-DOTA-Trastuzumab (~9.25 GBq each, equivalent to ~2 patient doses) with radiochemical yield (RCY) between 84 and 86% and radiochemical purities (RCP) >99%. The
in vitro
stabilities of both these radioimmunoconjugates (RICs) were retained up to 120 h post-radiolabeling, upon storage with L-ascorbic acid as stabilizer (concentration: ~ 220–240 μg/37MBq) at −20 °C. The ready-to-use formulation of clinical doses[
177
Lu]Lu-DOTA-Rituximab and [
177
Lu]Lu-DOTA-Trastuzumab has been successfully achieved by employing a single optimized protocol. While [
177
Lu]Lu-DOTA-Rituximab has exhibited a high degree of localization in retroperitoneal nodal mass of refractory lymphoma patient, high uptake of [
177
Lu]Lu-DOTA-Trastuzumab has been observed in metastatic breast carcinoma patient with multiple skeletal metastases.
Graphical abstract