Search Results (15)

Background: Radiolabeled compounds can serve as diagnostic or therapeutic agents depending on the characteristics of the isotopes used. IMPY (6-iodo-2-(4′-dimethylamino)-phenyl-imidazo[1,2-a]pyridine) is a lipophilic derivative of thioflavin-T, designed to function as a tracer when labeled with radioactive iodine. While it has been primarily studied for imaging applications, its potential therapeutic effects when labeled with iodine-125 (¹²⁵I) remain to be explored. Methods: In this study, IMPY was synthesized and labeled with ¹²⁵I for therapeutic purposes. Three different labeling methods were employed: isotope exchange reaction, redox reaction, and the Iodogen technique. The radiochemical yield of each method was determined to identify the most effective approach. Additionally, the effects of ¹²⁵I-IMPY on neuroblastoma cells were evaluated by assessing its toxicity and cellular uptake. Results: The radiochemical yields for the isotope exchange reaction, redox reaction, and Iodogen technique were found to be 0.96%, 10.74%, and 96.52%, respectively. The Iodogen technique exhibited the highest yield, exceeding 90% even after 48 h, making it the most efficient method. Furthermore, the impact of ¹²⁵I-IMPY on neuroblastoma cells was analyzed, revealing significant cellular uptake and potential therapeutic effects. Conclusions: This study demonstrated that the Iodogen technique is the most effective method for labeling IMPY with ¹²⁵I. The high labeling efficiency and observed cellular effects suggest that ¹²⁵I-IMPY could be considered not only as a tracer but also as a potential therapeutic agent for neuroblastoma. Further studies are needed to explore its full therapeutic potential and mechanism of action. Full article

Halide perovskite materials have broad prospects for applications in various fields such as solar cells, LED devices, photodetectors, fluorescence labeling, bioimaging, and photocatalysis due to their bandgap characteristics. This study compiled experimental data from the published literature and utilized the excellent predictive capabilities, low overfitting risk, and strong robustness of ensemble learning models to analyze the bandgaps of halide perovskite compounds. The results demonstrate the effectiveness of ensemble learning decision tree models, especially the gradient boosting decision tree model, with a root mean square error of 0.090 eV, a mean absolute error of 0.053 eV, and a determination coefficient of 93.11%. Research on data related to ratios calculated through element molar quantity normalization indicates significant influences of ions at the X and B positions on the bandgap. Additionally, doping with iodine atoms can effectively reduce the intrinsic bandgap, while hybridization of the s and p orbitals of tin atoms can also decrease the bandgap. The accuracy of the model is validated by predicting the bandgap of the photovoltaic material MASn_1−xPb_xI₃. In conclusion, this study emphasizes the positive impact of machine learning on material development, especially in predicting the bandgaps of halide perovskite compounds, where ensemble learning methods demonstrate significant advantages. Full article

The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [^131I]Iodine-α-mangostin ([¹³¹I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [¹³¹I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including −20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [¹³¹I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [¹³¹I]I-AM has an RCP above 90% after three days of storage at −20 °C. A significant difference was obtained between [¹³¹I]I-AM uptake in T47D and Vero cells. Based on these results, [¹³¹I]I-AM has been prepared with high RCP, stable at −20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [¹³¹I]I-AM as a diagnostic and therapeutic agent for breast cancer. Full article

A new rapid iodination reagent, N¹,N³,N⁵-tris[(2,4,6-trimethylpyridine)iodo(I)]-2,4,6-triphenyl-s-triazine trihexafluorophosphate, was synthesized in a modification of the established synthesis of 2,4,6-triiodo-3,5-dimethylphenol in the presence of bis(2,4,6-trimethylpyridine)iodo(I) hexafluorophosphate and used for the precise post-modification of mono- and trisubstituted phenyl compounds. We performed triple iodinations with our new phenyl-based compounds as a proof of principle of selected types of phenols, ß-sympatholytic agents and their spin-labeled derivatives, which can be employed in electron paramagnetic resonance (EPR) spectroscopy. The new rapid iodination reagent can be employed with high reactivity and regioselectivity. Full article

Purpose: A new PET radiotracer ¹⁸F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure–activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of ¹⁸F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer–NET interaction, whereby a T-shaped π–π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors. Full article

We have previously described the remarkable capacity of radioiodinated alkyl phospholipids to be sequestered and retained by a variety of tumors in vivo. We have already established the influence of certain structural parameters of iodinated alkyl phospholipids on tumor avidity, such as stereochemistry at the sn-2 carbon of alkylglycerol phosphocholines, meta-or para-position of iodine in the aromatic ring of phenylalkyl phosphocholines, and the length of the alkyl chain in alkyl phospholipids. In order to determine the additional structural requirements for tumor uptake and retention, three new radioiodinated alkylphospholipid analogs, 2–4, were synthesized as potential tumor imaging agents. Polar head groups were modified to determine structure-tumor avidity relationships. The trimethylammonio group in 1 was substituted with a hydrogen atom in 2, an ammonio group in 3 and a tertiary butyl group in 4. All analogs were separately labeled with iodine-125 or iodine-124 and administered to Walker 256 tumor-bearing rats or human PC-3 tumor-bearing SCID mice, respectively. Tumor uptake was assessed by gamma-camera scintigraphy (for [I-125]-labeled compounds) and high-resolution micro-PET scanning (for [I-124]-labeled compounds). It was found that structural modifications in the polar head group of alkyl phospholipids strongly influenced the tumor uptake and tissue distribution of these compounds in tumor-bearing animals. Phosphoethanolamine analog 3 (NM401) displayed a very slight accumulation in tumor as compared with phosphocholine analog 1 (NM346). Analogs 2 (NM400) and 4 (NM402) lacking the positively charged nitrogen atom failed to display any tumor uptake and localized primarily in the liver. This study provided important insights regarding structural requirements for tumor uptake and retention. Replacement of the quaternary nitrogen in the alkyl phospholipid head group with non-polar substituents resulted in loss of tumor avidity. Full article

Natural compounds provide precursors with various pharmacological activities and play an important role in discovering new chemical entities, including radiopharmaceuticals. In the development of new radiopharmaceuticals, iodine radioisotopes are widely used and interact with complex compounds including natural products. However, the development of radiopharmaceuticals from natural compounds with iodine radioisotopes has not been widely explored. This review summarizes the development of radiopharmaceuticals from natural compounds using iodine radioisotopes in the last 10 years, as well as discusses the challenges and strategies to improve future discovery of radiopharmaceuticals from natural resources. Literature research was conducted via PubMed, from which 32 research articles related to the development of natural compounds labeled with iodine radioisotopes were reported. From the literature, the challenges in developing radiopharmaceuticals from natural compounds were the purity and biodistribution. Despite the challenges, the development of radiopharmaceuticals from natural compounds is a golden opportunity for nuclear medicine advancement. Full article

Dopaminergic transporter (DAT) imaging with single photon emission computed tomography (SPECT) is used to diagnose Parkinson’s disease and to differentiate it from other neurodegenerative disorders without presynaptic dopaminergic dysfunction. The radioiodinated tropane alkaloids [¹²³I]FP-CIT and [¹²³I]β-CIT enable the evaluation of the integrity of DATs. Commonly, the labeling of these compounds is performed by electrophilic substitution of the alkylstannylated precursors with radioactive iodine and following purification by HPLC or solid phase extraction (SPE). This work presents the first radioiodination of β-CIT and FP-CIT with no carrier added [¹³¹I]NaI on a Scintomics GRP synthesis module. Free iodine-131 and impurities were removed by SPE over a C-18 Sep-Pak cartridge. We achieved a radiochemical yield of >75% and a radiochemical purity of >98% with both compounds. Our development of an automated synthesis on a commercially available synthesizer ensures robust and efficient labeling of [¹³¹I]FP-CIT and [¹³¹I]β-CIT starting with low concentrated radioiodine. Full article

Background: Boron neutron capture therapy requires a 2 mM ¹⁰B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [¹⁸F]fluoroBPA ([^18F]FBPA) as an agent to qualify for treatment. Precisely, [¹⁸F]FBPA must have at least a 3:1 tumor to background tissue ratio to qualify the patient for BNCT treatment. Normal, hyperplasia, and cancer thyroids capture iodine and several other large ions, including BF₄⁻, through a sodium-iodine symporter (NIS) expressed on the cell surface in normal conditions. In cancer, NIS is also expressed within the thyroid cell and is not functional. Methods: To visualize the thyroids and NIS, we have used a [¹⁸F]NaBF₄ positron emission tomography (PET) tracer. It was injected into the tail veins of rats. The [¹⁸F]NaBF₄ PET tracer was produced from NaBF₄ by the isotopic exchange of natural ¹⁹F with radioactive ¹⁸F. Rats were subject to hyperplasia and tumor-inducing treatment. The NIS in thyroids was visualized by immunofluorescence staining. The boron concentration was calculated from Standard Uptake Values (SUV) in the PET/CT images and from the production data. Results: 41 MBq, 0.64 pmol of [¹⁸F]NaBF₄ PET tracer that contained 0.351 mM, 53 nmol of NaBF₄ was injected into the tail vein. After 17 min, the peak activity in the thyroid reached 2.3 MBq/mL (9 SUV_max). The ^natB concentration in the thyroid with hyperplasia reached 381 nM. Conclusions: Such an incorporation would require an additional 110 mg/kg dose of [¹⁰B]NaBF₄ to reach the necessary 2 mM ¹⁰B concentration in the tumor. For future BNCT treatments of thyroid cancer, contrary to the ¹³¹I used now, there is no post-treatment radioactive decay, the patient can be immediately discharged from hospital, and there is no six-month moratorium for pregnancy. This method can be used for BNCT treatment compounds of the type R-BF_n, where 1 <= n <= 3, labeled with ¹⁸F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BF_n to reach the necessary ¹⁰B concentration for BNCT treatment in the tumor together, with [¹⁸F]R-BF_n for boron mapping. Full article

Glioblastoma multiforme (GBM), a common type of brain cancer, has a very poor prognosis. In general, viable GBM cells exhibit elevated phosphatidylserine (PS) on their membrane surface compared to healthy cells. We have developed a drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), that selectively targets cancer cells by honing in on this surface PS. To examine whether SapC-DOPS, a stable, blood–brain barrier-penetrable nanovesicle, could be an effective delivery system for precise targeted therapy of radiation, we iodinated several carbocyanine-based fluorescent reporters with either stable iodine (¹²⁷I) or radioactive isotopes (¹²⁵I and ¹³¹I). While all of the compounds, when incorporated into the SapC-DOPS delivery system, were taken up by human GBM cell lines, we chose the two that best accumulated in the cells (DiI (22,3) and DiD (16,16)). Pharmacokinetics were conducted with ¹²⁵I-labeled compounds and indicated that DiI (22,3)-SapC-DOPS had a time to peak in the blood of 0.66 h and an elimination half-life of 8.4 h. These values were 4 h and 11.5 h, respectively, for DiD (16,16)-SapC-DOPS. Adult nude mice with GBM cells implanted in their brains were treated with ¹³¹I-DID (16,16)-SapC-DOPS. Mice receiving the radionuclide survived nearly 50% longer than the control groups. These data suggest a potential novel, personalized treatment for a devastating brain disease. Full article

Carboxylic acids and their derivatives are readily available from both natural and synthetic sources. Apart from being used as direct substrates in the functional transformation, aryl carboxylic acids have found more applications in aromatic functionalization, especially in decarboxylation coupling reactions. Microwave-assisted protodecarboxylation and decarboxylative iodination of aromatic carboxylic acids were achieved with excellent yields in the presence of Ag₂CO₃ catalyst and K₂S₂O₈. These reactions will be helpful for better understanding of decarboxylation-related coupling reactions and also have the potential of being used as a practical labeling method to synthesize regioselective deuterium and iodine-labelled compounds for chemical, biological, and medicinal research. Full article

Dicarba-closo-dodecaboranes, commonly known as carboranes, possess unique physico-chemical properties and can be used as hydrophobic moieties during the design of new drugs or radiotracers. In this work, we report the synthesis of two analogues of 2-(4-aminophenyl)benzothiazole (a compound that was found to elicit pronounced inhibitory effects against certain breast cancer cell lines in vitro) in which the phenyl ring has been substituted by a m-carborane cage. Two different synthetic strategies have been used. For the preparation of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-benzo-thiazole, the benzothiazole group was first introduced on one of the cluster carbon atoms of m-carborane and the amine group was further attached in three steps. For the synthesis of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-6-hydroxybenzothiazole, iodination was performed before introducing the benzothiazole group, and the amino group was subsequently introduced in six steps. Both compounds were radiolabelled with carbon-11 using [¹¹C]CH₃OTf as the labelling agent. Radiolabelling yields and radiochemical purities achieved should enable subsequent in vitro and in vivo investigations. Full article

Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities of current drug therapy. However, the efficacy of these strategies, in particular “personalized medicine”, depends on precise information about individual target expression rates. Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology and thus bridges current knowledge to the clinical use. Moreover, nuclear medicine techniques provide therapeutic applications with tracers that behave like the diagnostic tracer. The advantages of radioiodination, still the most versatile radiolabeling strategy, and other labeled compounds comprising covalently attached radioisotopes are compared to the use of chelator-protein conjugates that are complexed with metallic radioisotopes. With the techniques using radioactive isotopes as a reporting unit or even the therapeutic principle, care has to be taken to avoid cleavage of the radionuclide from the protein it is linked to. The tracers used in molecular imaging require labeling techniques that provide site specific conjugation and metabolic stability. Appropriate choice of the radionuclide allows tailoring the properties of the labeled protein to the application required. Until the event of positron emission tomography the spectrum of nuclides used to visualize cellular and biochemical processes was largely restricted to iodine isotopes and 99m-technetium. Today, several nuclides such as 18-fluorine, 68-gallium and 86-yttrium have fundamentally extended the possibilities of tracer design and in turn caused the need for the development of chemical methods for their conjugation. Full article

Among the currently available positron emitters suitable for Positron Emission Tomography (PET), ¹²⁴I has the longest physical half-life (4.2 days). The long half-life and well-investigated behavior of iodine in vivo makes ¹²⁴I very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel ¹²⁴I labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological functions, and genetic deficiencies of such functions require pharmacological replacement, the efficacy of which must be properly and non-invasively evaluated. These enzymes, even though their natural substrates are mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric acid. The availability of [¹²⁴I]iodinated substrates is expected to provide a PET-based method for measuring their activity in vivo. The currently available methods of synthesis of iodinated arylsulfates usually require either introducing of a protected sulfate ester early in the synthesis or introduction of sulfate group at the end of synthesis in a separate step. The described method gives the desired product in one step from an aryl-alkyl cyclic sulfate. When treated with iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl center and gives the desired arylsulfate monoester. Full article

The use of radiopharmaceuticals for molecular imaging of biochemical and physiological processes in vivo has evolved into an important diagnostic tool in modern nuclear medicine and medical research. Positron emission tomography (PET) is currently the most sophisticated molecular imaging methodology, mainly due to the unrivalled high sensitivity which allows for the studying of biochemistry in vivo on the molecular level. The most frequently used radionuclides for PET have relatively short half-lives (e.g. ¹¹C: 20.4 min; ¹⁸F: 109.8 min) which may limit both the synthesis procedures and the time frame of PET studies. Iodine-124 (¹²⁴I, t_1/2 = 4.2 d) is an alternative long-lived PET radionuclide attracting increasing interest for long term clinical and small animal PET studies. The present review gives a survey on the use of ¹²⁴I as promising PET radionuclide for molecular imaging. The first part describes the production of ¹²⁴I. The second part covers basic radiochemistry with ¹²⁴I focused on the synthesis of ¹²⁴I-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the future prospective of using the long-lived positron emitter ¹²⁴I in the field of organic PET chemistry and molecular imaging. Full article