Review on 99mTc radiopharmaceuticals with emphasis on new advancements

Duatti, Adriano

doi:10.1016/j.nucmedbio.2020.05.005

Cited by 100 publications

(104 citation statements)

References 100 publications

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“…Thus, the development of novel 99m Tc-labeled norfloxacin derivatives as bacterial infection imaging agents has great significance. Generally, the majority of 99m Tc radiopharmaceuticals are designed through a bifunctional approach [32]. There are three sections (a pharmacophore, a chelating group, and a linking group) in each ligand, which are used to prepare the 99m Tc-labeled bifunctional radiopharmaceuticals.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

et al. 2021

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To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.

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Section: Discussionmentioning

confidence: 99%

Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

et al. 2021

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“…Technetium-99m ( 99m Tc) is one of the major radioisotopes widely used for clinical single-photon emission computed tomography (SPECT) imaging because it emits gamma rays with a photon energy of 141-keV, which is suitable for detection by the SPECT scanner, and it is easily produced by a molybdenum-99/technetium-99m generator 1 . To radiolabel 99m Tc, many chelating moieties have been developed and used widely 2 – 4 .…”

Section: Introductionmentioning

confidence: 99%

Development of a hydroxamamide-based bifunctional chelating agent to prepare technetium-99m-labeled bivalent ligand probes

Shimizu

Ando

Iikuni

et al. 2021

Sci Rep

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Hydroxamamide (Ham) is a thiol-free chelating agent that forms technetium-99m (99mTc)-complexes with a metal-to-ligand ratio of 1:2 under moderate reaction conditions. Therefore, Ham-based chelating agents will produce 99mTc-labeled compounds with a bivalent targeting scaffold. For their universal usage, we developed a novel Ham-based bifunctional chelating agent, “Ham-Mal”, with a maleimide group that can easily conjugate with a thiol group, for to preparing 99mTc-labeled bivalent ligand probes. Ham-Mal was synthesized by a four-step reaction, and then reacted with cysteine or c(RGDfC) to produce Ham-Cys or Ham-RGD. These precursors were reacted with 99mTcO4- for 10 min under room temperature to obtain 99mTc-(Ham-Cys)2 and 99mTc -(Ham-RGD)2. The cellular uptake level of 99mTc-(Ham-RGD)2 by U87MG (high Integrin ɑvβ3 expression) cells was significantly higher than that by PC3 (low Integrin ɑvβ3 expression) cells at 60 min after the incubation, and the uptake was significantly suppressed by pre-treatment for 15 min with excess c(RGDfK) peptide. In the in vivo study with U87MG/PC3 dual xenografted BALB/c-nu mice, the radioactivity of U87MG tumor tissue was significantly higher than that of PC3 tumor tissue at 360 min after the administration of 99mTc-(Ham-RGD)2. These results suggest Ham-Mal may have potential as a bifunctional chelating agent for 99mTc-labeled bivalent ligand probes.

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“…However, the availability and production costs of these radionuclides may hinder their rapid clinical transformation and popularization. In this situation, 99m Tc-labeled sdAbs can be translated into clinical application with more ease, thanking to the ideal properties and popularity of 99m Tc radionuclide [42].…”

Section: Discussionmentioning

confidence: 99%

First-in-human Study of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer

Zhao

Liu

Xing

et al. 2021

Preprint

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Background: Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy. HER2 expression in a complex environment, such as in a heterogenous tumor, makes precise assessment difficult using current methods. Therefore, we developed a novel 99mTc-labeled anti-HER2-single domain antibody (99mTc-NM-02) as a molecular imaging tracer for non-invasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in breast cancer patients.Methods: A lead compound (NM-02) was screened from a library of hexahistidine-tagged anti-HER2-single domain antibodies and labeled with 99mTc for the preparation of 99mTc-NM-02 tracer. Ten women with breast cancer were administered 99mTc-NM-02 at a mean dose of 458 ± 37 MBq (406−510 MBq), corresponding to 100 μg of NM-02. Whole-body and local SPECT/CT images were acquired at 1 and 2 h post-administration to investigate the tumor-targeting potential in primary and metastatic lesions. Additional images were acquired at 10 min, 3 h, and 24 h in three patients to calculate radiation dosimetry. Physical evaluation and blood analysis were performed for safety assessment.Results: No drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid, but only background levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10−3 mSv/MBq, and tracer uptake was visually observed in primary tumors and metastases. Owing to the fast clearance of the tracer, we were able to sufficiently discern uptake over normal background in both primary lesions and metastases within 2 h after injection. A maximal standard uptake value of 1.5 could be a reasonable cutoff for determining HER2 positivity using SPECT/CT imaging.Conclusions: Our 99mTc-NM-02 tracer can be safely used for imaging in breast cancer patients with reasonable radiation doses, favorable biodistribution and imaging characteristics. 99mTc-NM-02 SPECT imaging may provide an accurate and non-invasive method to detect HER2 status in breast cancer patients.Trial registration: ClinicalTrials.gov, NCT04040686. Registered 30 July 2019. https://clinicaltrials.gov/ct2/show/NCT04040686.

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Review on 99mTc radiopharmaceuticals with emphasis on new advancements

Cited by 100 publications

References 100 publications

Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

Development of a hydroxamamide-based bifunctional chelating agent to prepare technetium-99m-labeled bivalent ligand probes

First-in-human Study of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer

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