Radiochemistry,Production Processes,Labeling Methods,and ImmunoPET Imaging Pharmaceuticals of Iodine-124

Target-specific biomolecules, monoclonal antibodies (mAb), proteins, and protein fragments are known to have high specificity and affinity for receptors associated with tumors and other pathological conditions. However, the large biomolecules have relatively intermediate to long circulation half-lives (>day) and tumor localization times. Combining superior target specificity of mAbs and high sensitivity and resolution of the PET (Positron Emission Tomography) imaging technique has created a paradigm-shifting imaging modality, ImmunoPET. In addition to metallic PET radionuclides, ¹²⁴I is an attractive radionuclide for radiolabeling of mAbs as potential immunoPET imaging pharmaceuticals due to its physical properties (decay characteristics and half-life), easy and routine production by cyclotrons, and well-established methodologies for radioiodination. The objective of this report is to provide a comprehensive review of the physical properties of iodine and iodine radionuclides, production processes of ¹²⁴I, various ¹²⁴I-labeling methodologies for large biomolecules, mAbs, and the development of ¹²⁴I-labeled immunoPET imaging pharmaceuticals for various cancer targets in preclinical and clinical environments. A summary of several production processes, including ¹²³Te(d,n)¹²⁴I, ¹²⁴Te(d,2n)¹²⁴I, ¹²¹Sb(α,n)¹²⁴I, ¹²³Sb(α,3n)¹²⁴I, ¹²³Sb(³He,2n)¹²⁴I, ^natSb(α, xn)¹²⁴I, ^natSb(³He,n)¹²⁴I reactions, a detailed overview of the ¹²⁴Te(p,n)¹²⁴I reaction (including target selection, preparation, processing, and recovery of ¹²⁴I), and a fully automated process that can be scaled up for GMP (Good Manufacturing Practices) production of large quantities of ¹²⁴I is provided. Direct, using inorganic and organic oxidizing agents and enzyme catalysis, and indirect, using prosthetic groups, ¹²⁴I-labeling techniques have been discussed. Significant research has been conducted, in more than the last two decades, in the development of ¹²⁴I-labeled immunoPET imaging pharmaceuticals for target-specific cancer detection. Details of preclinical and clinical evaluations of the potential ¹²⁴I-labeled immunoPET imaging pharmaceuticals are described here.     

Dynamics of Fluorescent Dyes Attached to G‐Quadruplex DNA and their Effect on FRET Experiments

FRET spectroscopy is a promising approach for investigating the dynamics of G‐quadruplex DNA folds and improving the targeting of G‐quadruplexes by potential anticancer compounds. To better interpret such experiments, classical and replica‐exchange molecular dynamics simulations and fluorescence‐lifetime measurements are used to understand the behavior of a range of Cy3‐based dyes attached to the 3′ end of G‐quadruplex DNA. The simulations revealed that the dyes interact extensively with the G‐quadruplex. Identification of preferred dye positions relative to the G‐quadruplex in the simulations allows the impact of dye–DNA interactions on FRET results to be determined. All the dyes show significant deviations from the common approximation of being freely rotating and not interacting with the host, but one of the Cy3 dye analogues is slightly closer to this case.     

Elution profiles of lanthanides with α‐hydroxyisobutyric acid by ion exchange chromatography using fine resin

Experiments were carried out using a strong acid cation exchange resin with a particle size of 75–150 μm, termed as “fine resin” in hydrogen ion form for the elution of individual lanthanides Sm, Eu, Gd, Tb, and Dy that are produced as fission products in the spent nuclear fuel and generated in the effluent during reprocessing of spent nuclear fuel. Batch experiments were carried out to study the effect of concentration of nitric acid on distribution coefficient. The distribution coefficient values for these individual lanthanides were determined in nitric acid medium in the concentration range of 0.01–4.0 N. Uptake of each individual lanthanide by resin was increased with increased nitric acid concentration from 0.01 to 0.5 N and remained similar from 0.5 to 1.0 N and decreased thereafter up to 4.0 N. Column experiments were also carried out using the same resin to study the parameters like pH of the eluent, flow rate, and resin bed height under isocratic elution conditions for eluting lanthanide elements using α‐hydroxyisobutyric acid as eluent. The results of this study have indicated the possibility for the elution of individual lanthanides.     

Computational Studies on Intramolecular Cycloadditions of Azidoenynes and Azidobutenenitriles to Give 6H‐Pyrrolo[1,2‐c][1,2,3]triazoles and 5H‐Pyrrolo[1,2‐d]tetrazoles

Energetics of intramolecular cycloadditions of azidoenynes and azidobutenenitriles to give 6H‐pyrrolo[1,2‐c][1,2,3]triazoles and 5H‐pyrrolo[1,2‐d]tetrazoles have been calculated at the B3LYP/6.311++G(3df,3pd) level of theory in ideal gas and in H₂O as solvent. Stabilities of the corresponding anions, tautomers, and isomers are discussed. Transition states of the cyclization of parent compounds are determined at the same level of theory.     

A Cucurbit[8]uril 2:2 Complex with a Negative pKa Shift

A viologen derivative carrying a benzimidazole group ( V-P-I ²⁺; viologen–phenylene–imidazole V-P-I ) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pK_a, by more than 1 pH unit, contrasting with the positive pK_a shift usually observed for CB-based complexes. Whereas 2:2 complex protonation is unclear by NMR, silver cations have been used for probing the accessibility of the imidazole groups of the 2:2 complexes. The protonation capacity of the buried imidazole groups is reduced, suggesting that CB[8] could trigger proton release upon 2:2 complex formation. The addition of CB[8] to a solution containing V-P- I ³⁺ indeed released protons as monitored by pH-metry and visualized by a coloured indicator. This property was used to induce a host/guest swapping, accompanied by a proton transfer, between V-P-I ³⁺ ⋅ CB[7] and a CB[8] complex of 1-methyl-4-(4-pyridyl)pyridinium. The origin of this negative pK_a shift is proposed to stand in an ideal charge state, and in the position of the two pH-responsive fragments inside the two CB[8] which, alike residues engulfed in proteins, favour the deprotonated form of the guest molecules. Such proton release triggered by a recognition event is reminiscent of several biological processes and may open new avenues toward bioinspired enzyme mimics catalyzing proton transfer or chemical reactions.     

A Novel One Pot Photochemical Synthesis of Substituted 2-oxo-1,2,2a,11-Tetrahydro-Benzo [3,4-a] Imidazolo [3,4-a] Quinolines

On irradiation with sunlight N-α-cyanoamines (I) undergo a novel cyclisation with the induction of one methylene group from the solvent (methanol) to give new benzoimidazoloquinolines (II) in good yield.     

STRATIFICATION IN EMULSION FILMS

Formation of films possessing a layered or stratified structure has been observed with foam films from liquid crystals, from concentrated surfactant solutions and in liquid layers on the surface of water. The stratifying films have a structure similar to that of the smectic phase which soaps are known to form in the bulk solution at high concentrations. The repeating units of which such films are built are the so-called black films: each unit consists of two surfactant layers interleaved by a thin aqueous core. In the study presented here we have observed that stratification can also take place in emulsion films from concentrated aqueous surfactant solutions. We have compared these results with those obtained for foam films using the same surfactant, i.e. sodium dodecylsulfate.