Preparation of 212 Pb-labeled monoclonal antibody using a novel 224 Ra-based generator solution

Abstract

The current work demonstrates a novel method of producing Pb-based radioimmunoconjugates from aRa-solution, which may be simpler and less time-consuming for the end user compared with the method established for use in clinical trials of Pb-TCMC-trastuzumab.

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [212Pb]Pb‐NG001 for prostate cancer

“…The 224 Ra was free of 228 Ra, 226 Ra and 223 Ra as demonstrated by decay analyses , and thereby, is carrier‐free. The details of the 224 Ra/ 212 Pb‐solution generator setup have been described elsewhere . Radioactive samples were measured on a Cobra II Autogamma counter (Packard Instrument Company, Downer Grove, Illinois) and Hidex Automatic Gamma counter (Hidex Oy, Turku, Finland) with the counting window setting from 60 to 110 keV.…”

“…Radium‐224 was extracted from a generator column containing actinide resin (Eichrom Technologies, Lisle, Illinois) with immobilized 228 Th (Eckert & Ziegler, Braunschweig, Germany) by eluting with 1 M HCl . The 224 Ra was free of 228 Ra, 226 Ra and 223 Ra as demonstrated by decay analyses , and thereby, is carrier‐free.…”

Antitumor Activity of Novel Bone-seeking, α-emitting 224Ra-solution in a Breast Cancer Skeletal Metastases Model

“…Radium-224 was extracted from a generator based on 228 Th (Eckert & Ziegler, Braunschweig, Germany) immobilized on a DIPEX ® (Eichrom Technologies LLC, Lisle, IL, USA) actinide resin (18). It was purified and found with no traces of 228 Th (18). The details of the 224 Ra generator setup have been described elsewhere.…”

“…Since 224 Ra decay has a modest γ-emission in an energy region with more abundant γ from daughter 212 Pb, 224 Ra activity was determined indirectly from the counts in the 70-80 keV or 60-110 keV windows. The details of the radioactivity measurements have been described elsewhere (18). A Capintec CRC-25R dose calibrator and Cobra II Autogamma counter (Packard Instrument, Downers Grove, II, USA) were used for radioactivity measurements.…”

“…As an alternative to EDTMP it is also possible to use a bifunctional chelating agent TCMC (1,4,7,10-tetra-(2-carbamoyl methyl)-cyclododecane) conjugated with a Figure 4B. Bottom of the boxes (A, B) monoclonal antibody (for example, trastuzumab (31,32)) that can be added to the 224 Ra-solution in equilibrium with 212 Pb to scavenge 212 Pb (16,18). Upon administration, the antibody moiety of 212 Pb-TCMC-trastuzumab binds with high affinity to the extracellular domain of human epidermal growth factor receptor 2 (HER2) which is overexpressed on the surface of breast cancers (31,32).…”