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The 2‐nitroimidazole based 99mTc‐radiopharmaceuticals are widely explored for imaging tumor hypoxia. Radiopharmaceuticals for targeting hypoxia are often lipophilic and therefore, show significant uptake in liver and other vital organs. In this context, lipophilic radiopharmaceuticals with design features enabling faster clearance from liver may be more desirable. A dipicolylamine‐NCS bifunctional chelator that could generate a thiourea‐bridge up on conjugation to primary amine bearing molecule was used to synthesize a 2‐nitroimidazole‐dipicolyl amine ligand for radiolabeling with 99mTc(CO)3 core. Corresponding Re(CO)3‐analogue was prepared to establish the structure of 2‐nitroimidazole‐99mTc(CO)3 complex prepared in trace level. The 2‐nitroimidazole‐99mTc(CO)3 complex showed a hypoxic to normoxic ratio of ~2.5 in CHO cells at 3 h. In vivo, the complex showed accumulation and retention in tumor with high tumor to blood and tumor to muscle ratio. The study demonstrated the utility of metabolizable thiourea‐bridge in 2‐nitroimidazole‐99mTc(CO)3 complex in inducing faster clearance of the radiotracer from liver. The dipicolylamine‐NCS bifunctional chelator reported herein can also be used for radiolabeling other class of target specific molecules with 99mTc(CO)3 core. [ABSTRACT FROM AUTHOR]

Objective The incidence of inoperable hepatocellular carcinoma (HCC) with/without malignant portal vein thrombosis (PVT) is increasing in India for the last decade; thus, Bhabha Atomic Research Centre (BARC), Mumbai, India, developed diethydithiocarbamate (DEDC), a new transarterial radionuclide therapy (TART) agent. 188 Re-N-DEDC lipiodol is an emerging radiotherapeutic agent for inoperable HCC treatment due to its simple and onsite labeling procedure, cost-effectiveness, and least radiation-induced side effects. This study aimed to evaluate in-vivo biodistribution and clinical feasibility of 188 Re-N-DEDC lipiodol TART in HCC and optimization of labeling procedure to assess post-labeling stability and radiochemical yield of labeled lipiodol with 188 Re-N-DEDC complex. Materials and Methods DEDC kits were obtained as gift from BARC, Mumbai. Therapy was given to 31 HCC patients. Post-therapy planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were performed to see tumor uptake and biodistribution. Clinical feasibility and toxicity were decided by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0). Statistical Analysis Descriptive statistics was done for data using SPSS v22. Values was expressed as mean ± standard deviation or median with range. Results Post-therapy planar and SPECT/CT imaging showed radiotracer localization in hepatic lesions. Few patients showed lungs uptake due to hepato-pulmonary shunt (lung shunt < 10%). Maximum clearance was observed through urinary tract with very less elimination through hepatobiliary route due to slow rate of leaching of tracer. No patient showed myelosuppression or any other long-term toxicity over median follow-up of 6 months. Mean overall % radiochemical yield of 188 Re-N-DEDC lipiodol was 86.04 ± 2.35%. The complex 188 Re-N-DEDC was found to be stable at 37°C under sterile condition over a period of 1 hour without any significant change on the % radiochemical purity (90.83 ± 3.24%, 89.78 ± 3.67%, 89.22 ± 3.77% at 0, 0.5, 1 hours, respectively). Conclusion Human biodistribution showed very high retention of radiotracer in hepatic lesions with no long-term toxicity with this therapy. The kit preparation procedure is ideally suited for a busy hospital radio-pharmacy. By this procedure, 188 Re-N-DEDC lipiodol can be prepared in high radiochemical yield within a short time (∼45 minutes). Thus, 188 Re-N-DEDC lipiodol can be considered for TART in advanced and/or intermediate HCC. [ABSTRACT FROM AUTHOR]

123I‐Iodophenylpentadecanoic acid (IPPA) is a metabolic agent used in nuclear medicine for diagnosis of myocardial defects. Efforts are underway worldwide to develop a 99mTc substitute of the above radiopharmaceutical for the aforementioned application. Herein, we report synthesis and biodistribution studies of 99mTc labeled fatty acids (8, 11, and 15 carbons) obtained via "click chemistry" for its potential use in myocardial imaging. ω‐Bromo fatty acids (8C/11C/15C) were synthetically modified at bromo terminal to introduce a heterocyclic triazole with glycine sidearm in a five step procedure. Modified fatty acids were subsequently radiolabeled with preformed [99mTc(CO)3]+ synthon to yield the desired fatty acid complexes which were evaluated in Swiss mice. All the radiolabeled complexes were obtained with radiochemical purities >80%, as characterized by HPLC. Biodistribution studies of all three complexes in Swiss mice showed myocardial uptake of ~6‐9% ID/g at 2 minutes post‐injection, close to*I‐IPPA (~9% ID/g). Complexes exhibited significant retention in the myocardium up to 30 minutes (~1% ID/g) but were lower to the standard agent (~7% ID/g). Similar uptake of activity in myocardium for the newly synthesized complexes in comparison to 125I‐IPPA along with favorable in vivo pharmacokinetics merits potential for the present "click" design of complexes for myocardial imaging. 123I‐Iodophenylpentadecanoic acid (IPPA) is a metabolic agent used for diagnosis of myocardial defects. Herein, we report 99mTc‐labeled fatty acids (8, 11, and 15 carbons) obtained via "click chemistry" as a rationale substitute. ω‐Bromo fatty acids were synthetically modified at ω terminal and radiolabeled via [99mTc(CO)3(H2O)3]+ synthon. Biodistribution of complexes in Swiss mice showed myocardial uptake similar to*I‐IPPA at 2 min pi with favorable in vivo pharmacokinetics which merits potential for the present "click" design of complexes for myocardial imaging. [ABSTRACT FROM AUTHOR]

Conventional 99mTc-radiopharmaceuticals for the detection of tumor hypoxia generally possess a single nitroimidazole moiety. Herein, we report the synthesis and evaluation of a 99mTc-complex with three-nitroimidazole moieties in an attempt to improve hypoxic cell detection. Isocyanide derivative of metronidazole (MetroNC) was synthesized and subsequently radiolabeled with [99mTc(CO)3(H2O)3]+ precursor complex, wherein the three labile water molecules were replaced with MetroNC ligand to form a pseudo-octahedral [99mTc(CO)3(MetroNC)3]+ complex. Analysis of corresponding Re(CO)3-analog prepared in macroscopic scale confirmed the formation of expected complex. Cyclic voltammetric studies of [Re(CO)3(MetroNC)3]+ complex showed no significant change in single-electron reduction potential (SERP) of MetroNC ligand (− 0.96 V) upon forming the [Re(CO)3(MetroNC)3]+ complex (− 0.90 V). In vitro studies in Chinese hamster ovary (CHO) cells showed three-fold preferential accumulation of [99mTc(CO)3(MetroNC)3]+ complex in hypoxic cells over normoxic cells. Biodistribution studies of [99mTc(CO)3(MetroNC)3]+ complex in Swiss mice bearing fibrosarcoma tumor showed tumor uptake and steady retention till 60 min post injection. Present study constitutes a novel design approach towards development of a 99mTc-radiopharmaceutical for hypoxia imaging application, which could be extended to other potential nitroimidazole ligands. [ABSTRACT FROM AUTHOR]

Rhenium-188-N-(DEDC) 2 /lipiodol (abbreviated as 188 ReN-DEDC, where DEDC = monoanionic diethyldithiocarbamate) is a clinically proven radiopharmaceutical for the therapy of unresectable hepatocellular carcinoma (HCC) through trans arterial radioembolization (TARE). A two-vial freeze-dried kit for the preparation of [ 188 ReN(DEDC) 2 ] complex using sodium perrhenate (Na 188 ReO 4 ) obtained from a commercial Tungsten-188/Rhenium-188 generator had been reported earlier. This method required addition of stipulated volume of glacial acetic acid into vial 1 by the user for efficient preparation of [ 188 ReN] 2+ intermediate. An error in this step can result in low radiochemical yield of [ 188 ReN] 2+ intermediate as well as sub-optimal pH of the reaction mixture for the second step, leading to poor radiochemical purity of 188 ReN-DEDC complex. In the present work, a solution to this problem was found by including an oxalate buffer of pH = 3 in vial 1, eliminating the need for the addition of glacial acetic acid by the user. This modification not only made the kits more user-friendly, it resulted in significant improvement in the kinetics of formation of [ 188 ReN] 2+ intermediate, wherein > 95% radiochemical purity could be achieved within 5 min incubation at ambient temperature. Moreover, the novel route for the preparation of [ 188 ReN] 2+ intermediate may be applied to any radiopharmaceutical based on 188 ReN-core. [ABSTRACT FROM AUTHOR]

We report the construction of a novel non-covalently held cucurbit[7]uril-heptamolybdate hybrid material for the first time, and demonstrate its application as a generator bed for the facile and efficient separation of the 99mTc radiotracer, which is in demand for several theranostic applications. [ABSTRACT FROM AUTHOR]

The PET radiopharmaceutical [18F]Fluromisonidazole ([18F]FMISO) is presently the agent of choice for the clinical imaging of tumor hypoxia. Considering the logistic advantages of 99mTc and wider availability of SPECT machines, a 99mTc-radiopharmaceutical for this purpose constitutes an attractive choice. In the work presented here, a misonidazole analogue was radiolabeled with 99mTc(CO)3 core and the complex was evaluated in Swiss mice bearing fibrosarcoma tumor. The results obtained are compared with the biodistribution of [18F]FMISO carried out in the same tumor-bearing animal model. Misonidazole-99mTc(CO)3 complex showed significant uptake and retention in tumor. Notably, the rate of clearance of misonidazole complex from the tumor was slower than that of [18F]FMISO. The maximum tumor/muscle ratio obtained with misonidazole-99mTc(CO)3 complex was significantly higher than that of [18F]FMISO. The study constitutes a positive step toward the development of a 99mTc-analogue of [18F]FMISO. [ABSTRACT FROM AUTHOR]

Introduction Hypoxia plays a negative role in the clinical management of cancer. Detection of hypoxic status of a cancer is important for selecting patients for hypoxia directed therapy. Though [18 F]fluoromisonidazole ([18 F]FMISO), a PET radiopharmaceutical, is presently being used in the clinic for the detection of hypoxia, considering the logistical advantages of 99mTc and wider availability of SPECT scanners, a radiopharmaceutical based on this isotope may find wider applicability. Methods Nine nitroimidazole (2-, 4- and 5-nitroimidazole) ligands were synthesized and radiolabeled using [99mTc(CO)3(H2O)3]+ precursor to obtain a group of complexes possessing different single electron reduction potential (SERP), overall charge and lipophilicity, the three attributes which decide the efficacy of the complex to detect hypoxic cells in vivo. The nitroimidazole-99mTc(CO)3 complexes as well as [18 F]FMISO were evaluated in fibrosarcoma tumor bearing mice. Results The 99mTc(CO)3 complexes of nitroimidazole iminodiacetic acid (IDA) showed better tumor uptake and retention than nitroimidazole diethylenetriamine (DETA) and nitroimidazole aminoethylglycine (AEG) complexes. Tumor uptake observed with [18 F]FMISO was higher than any of the nitroimidazole-IDA- 99mTc(CO)3 complexes. However, [18 F]FMISO clearance from tumor was found to be faster compared to 2-nitroimidazole-IDA-99mTc(CO)3 complex. Observed tumor uptake and retention of the radiotracers evaluated could be correlated to its blood clearance pattern and SERP. Conclusions Results of the present study indicated that uptake of the radiotracer in tumor is closely associated with its rate of clearance from blood. The study also indicated that along with SERP, clearance of radiotracer from blood (net effect of charge and lipophilicity) is a critical factor which decides the in vivo efficacy of the hypoxia detecting radiopharmaceutical. [ABSTRACT FROM AUTHOR]