Development of ¹⁷⁰Tm‐DOTA‐cetuximab for radioimmunotherapy

Abstract

Thulium‐170 [T1/2 = 128.4 days, Eβ(max) = 968 keV, Eγ = 84 keV (3.26%)] has radionuclidic properties suitable for use in therapy. 170Tm can be produced by a relatively feasible route involving thermal neutron bombardment on natural Tm(NO3)3 (100% 169Tm) in medium flux research reactors. The combination of beta‐particle emission of Tm‐170 with therapeutic properties of C225 monoclonal antibody (cetuximab) as well as optimization studies for future Tm‐167 labeling was targeted in this study. Conjugated cetuximab was obtained by the addition of 0.5 ml of a cetuximab pharmaceutical solution (1 mg, in phosphate buffer, pH 7.8) to a glass tube pre‐coated with in situ prepared 1,4,7,10‐tetraazacyclododecane‐N,N,N,N‐tetraacetic acid mono‐(N‐hydroxysuccinimidyl) ester (DOTA‐NHS) (~5 mg) at 25°C. Cetuximab was labeled with 170Tm‐Thulium chloride (100 MBq) after conjugation with DOTA‐NHS in 2–3 h (radiochemical purity >99%, instant thin‐layer chromatography, specific activity = 77–385 TBq/mmol). Biodistribution studies in wild‐type rats for free Tm‐170 and the radioimmunoconjugate were performed to determine the distribution up to 72 h. A comparative time‐frame study was performed for critical organs for both radiochemical species. The major organs of accumulation were shown to be the lung, liver, and spleen, respectively. Copyright © 2012 John Wiley & Sons, Ltd.

Active targeting of gold nanoparticles as cancer therapeutics

“…58 The decision to radiolabel the antibody itself likely stems from the fact that radiolabelled cetuximab has been widely investigated as an agent for radioimmunotherapy. [59][60][61] These AuNPs were seen to display a targeted decrease in cell viability of A549 cells, with this cytotoxicity higher than that of 131 I at the same dosage, 58 highlighting the ability of AuNPs to increase the potency of a payload.…”

Radiochemical processing of nuclear-reactor-produced radiolanthanides for medical applications

“…This medical radiolanthanide will not be discussed in more detail in this review since 149 Tb cannot be produced via neutron irradiation in a nuclear reactor. 4.2. b À emitting radiolanthanides b À particle emitting isotopes for medical use are more widespread throughout the lanthanide series, including 143 Pr, 149 Pm, 153 Sm, 161 Tb, 165 Dy, 166 Ho, 169 Er, 170 Tm and 177 Lu. Each of them emits b À particles with different energies, resulting in different tissue penetration depths, i.e.…”

“…Emphasis is put on those radiolanthanides that are of highest medical relevance and are produced in a nuclear research reactor, i.e. Pr, 149 Pm, 153 Sm, 165 Dy, 161 Tb, 166 Ho, 169 Er, 170 Tm and 177 Lu. In addition, production methods for 47 Sc and 90 Y using a nuclear reactor are described briefly as well, because the chemical properties of scandium and yttrium are very similar to those of the lanthanides.…”

“…Another example is the presence of harmful side products, like long-lived isotopes (e.g. 154 Eu in 153 Sm), which have to be removed prior to use, even when present in low quantities. National and international organizations (e.g.…”

Application of a tailor-made polymer as a selective and sensitive colorimetric sensor for reliable detection of trace levels of uranyl ions in complex matrices

“…in separation, preconcentration and purification processes with regard to metal ions including transition elements [28], actinides [29], lanthanides [30], and noble metals in diverse matrices [31]. Ion-imprinted polymers have various applications, e.g.…”