Lumiphore’s macrocyclic chelation technology facilitates bright luminescent and stable metal ion complexes suitable for ultrasensitive detection. The company has developed a hydroxyisophthalamide macrocyclic BFC to bind and sensitize the luminescent metal terbium (Lumi4®-Tb). Facilitating time-gated reporting that outlasts the fluorescence of other molecules, resulting in vastly improved signal-to-noise. Both Lumi4®-Tb and Lumi804™-Eu are used in high value homogenous assays.
Lumiphore’s chelation technology meets the unmet need of rapid, stable chelation at or below physiological temperature with exceptional in-vivo stability for a wide range of radionuclides. Our mBFC technology is the next generation of chelation technology with fundamental features surpassing DOTA, DTPA, and DFO for radiotheranostic applications. Our proprietary chelation platform, paired with an appropriate targeting vector (such as an antibody, antibody fragment, protein or peptide), facilitates reliable localization of radionuclides to biological sites of interest. The company’s proprietary ‘Raymond Chelation Technology’ reworks Nature’s siderophore components into macrocyclic Bi-Functional Chelators (mBFCs), suitable for: attachment to targeting vectors,quick and stable binding radiometals of interest,simple chelation protocol at physiological temperature,one mBFC, many metal compatibility, and high TRF intensity fluorescent reporting capabilities in vitro for cell based discovery. These macrocyclic BFCs are best-in-class materials for reliable incorporation and delivery of metal ion payloads in medicine. Lumiphore, we have linked multiple copies of these bidentate chelators together into larger macrocyclic molecular frameworks, collectively described as macrocyclic BiFunctional Chelators. The bifunctional characteristic being both metal binding and disease targeting elements achieved through covalent chemistry options of the mBFC. Decades of experience designing these molecular frameworks, has resulted in the preorganization of bidentate chelators for metal ion binding. Preorganization greatly enhances the stability of the chelator-metal ion complexes. The macrocyclic BFCs can be conceptualized as molecular ‘cages’ that inhibit the release of the metal ion, once bound. With unsurpassed ease of use, high stability, and rapid chelation, these macrocyclic BFCs form the basis of the company’s chelation technology, and set the new standard for use of radionuclides in diagnostic and therapeutic applications. The benefits of the company’s mBFCs for TRTs are: Ease-of-Use• radiolabeling performed under physiologic conditions & mild temperatures • preserve sensitive targeting agents • ease-of-use for the radio-pharmacy Radio-metal Tightly Held• delivery & dosage maximized by chelators holding the radio-metal during delivery effectively minimizing side effects of released radiometal Delivering radio-active therapeutic potency• Potential to kill tumor cells with low-number target receptor expression. Enables fluorescent tracking• chelators can be used to develop assays for bio-distribution, PK, metabolism, etc. Multiple covalent chemistries• mBFCs can be provided with many different linker chemistry for targeting agent labeling • includes NHS ester, maleimide, isothiocyanate, amine, carboxylate, carbonyl, and others Compatible with all targeting agent classes• ideal for targeting agents with secondary structures or thermal sensitivities such as antibodies, Fabs, scFvs, minibodies, diabodies, etc. • easily coupled with peptides, peptoids, nucleic acids, oligos, small molecules, hormones and other targetingagents
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Introducing Lumi804 – Next Generation Radiometal Chelation Lumiphore has introduced its new 1,2-HOPO macrocyclic BFC for TRT use dubbed Lumi804 TM. This single molecule chelate can handle a variety of radio-metals and is available for licensing and collaboration opportunities. One mBFC – Multiple Radiometals Retaining a small but important degree of flexibility is a feature of all of our macrocyclic BFCs. Shown above are the crystal structures of Eu-, Lu- and Zr-Lumi804 parent mBFCs, demonstrating how a wide range of metal ion sizes can all be accommodated by a single partially flexible chelator. Additionally, Europium is highly sensitized by Lumi804 with a quantum yield approaching 30% - highest available for aqueous environment. This an other core features are enabling in vitro assay and analysis utilizing Time Resolved Fluorescence (TRF) or TR-FRET. Stable In-Vivo Chelation Complex stability was probed with 1:1 metal:Lumi804 complexes, HPLC purified, incubated in 250 mM DTPA at pH = 7.4 for up to 18 days. As Lumi804 has a characteristic absorption spectra differentiating the Prescence or absence of chelated metal, this was monitored for up to 18 days at 24C. Lumi804-Eu binds and sensitizes the luminescent metal europium, which emits at different wavelength than terbium, permitting simultaneous multi-channel fluorescent testing. Both Lumi4®-Tb and Lumi804™-Eu are used in high value homogenous assays.
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