Synthesis and evaluation of a Ga-labeled iodinated benzamide derivative as a PET imaging agent for malignant melanoma.

Malignant melanoma is a highly aggressive skin cancer with increasing prevalence worldwide. The 5-year survival rate for localized malignant melanoma is 90%, but this drops to 6% if metastasis has occurred at diagnosis. Current positron emission tomography (PET) imaging probes, such as 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG), show low sensitivity for metastatic melanoma, underscoring the need for new probes.

68Ga-labeled fluorinated benzamide derivatives for positron emission tomography imaging of melanoma.

Malignant melanoma tends to aggressively metastasize, resulting in it being a potentially lethal form of skin cancer with high mortality rates. The advanced stages of melanoma have a very poor prognosis because of the high tendency for metastasis, and there is therefore, a strong desire to develop efficient technology for the early detection of melanoma. The benzamide structure, which contains aromatic ring and amine group, exhibits a high affinity for melanin, making it a promising agent for targeting melanoma in diagnostic and therapeutic applications.

Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.

Purpose: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe.

Synthesis and evaluation of F-labeled procainamide as a PET imaging agent for malignant melanoma.

Malignant melanoma has an aggressive nature and a high metastatic propensity resulting in the highest mortality rate of any skin cancer. In this study, we synthesized F-labeled procainamide (PCA) for detection of melanoma using positron emission tomography (PET), and evaluated its biological characteristics. The non-decay-corrected radiochemical yield of F-PCA was 10-15% and its in vitro stability was over 98% for 2 h.

In vivo imaging of invasive aspergillosis with F-fluorodeoxysorbitol positron emission tomography.

Invasive aspergillosis is a critical complication in immunocompromised patients with hematologic malignancies or with viral pneumonia caused by influenza virus or SARS‑CoV‑2. Although early and accurate diagnosis of invasive aspergillosis can maximize clinical outcomes, current diagnostic methods are time-consuming and poorly sensitive. Here, we assess the ability of 2-deoxy-2-F-fluorosorbitol (F-FDS) positron emission tomography (PET) to specifically and noninvasively detect Aspergillus infections.

In situ x-ray-induced acoustic computed tomography with a contrast agent: a proof of concept.

X-ray-induced acoustic computed tomography (XACT) has shown great potential as a hybrid imaging modality for real-time non-invasive x-ray dosimetry and low-dose three-dimensional (3D) imaging. While promising, one drawback of the XACT system is the underlying low signal-to-noise ratio (SNR), limiting its in vivo clinical use. In this Letter, we propose the first use of a conventional x-ray computed tomography contrast agent, Gastrografin, for improving the SNR of in situ XACT imaging.

Multimodal Imaging-Based Potential Visualization of the Tumor Microenvironment in Bone Metastasis.

Bone metastasis (BM) is the most common malignant bone tumor and a significant cause of morbidity and mortality for patients with cancer. Compared to other metastatic organs, bone has unique characteristics in terms of the tumor microenvironment (TME). Precise assessments of the TME in BM could be an important step for developing an optimized management plan for patient care.

A Stepwise Approach Using Metastatic Lymph Node Ratio-Combined Thyroglobulin for Customization of [F]FDG-PET/CT Indication to Detect Persistent Disease in Patients with Papillary Thyroid Cancer.

We investigated whether an indication for [F]FDG-PET/CT to detect FDG-avid persistent disease (PD) could be identified precisely using the extent of metastatic lymph nodes (MLNs) and serum thyroglobulin (Tg) in papillary thyroid cancer (PTC) patients. This retrospective study included 429 PTC patients who underwent surgery and radioactive iodine (RAI) therapy. [F]FDG-PET/CT and serum Tg were evaluated just before RAI therapy.

Differences in diagnostic impact of dual-tracer PET/computed tomography according to the extrahepatic metastatic site in patients with hepatocellular carcinoma.

Objectives: We compared the diagnostic performance of C-11 acetate and F-18 fluorodeoxyglucose (FDG) PET/computed tomography (CT) for the detection of extrahepatic metastasis in patients with hepatocellular carcinoma (HCC) and evaluated whether the improvement in the diagnostic performance of dual tracer PET/CT differs by the metastatic site.

Methods: Fifty-eight patients who had extrahepatic metastasis on either C-11 acetate or F-18 FDG PET/CT were enrolled, and 193 metastatic lesions were analyzed in this retrospective study. The metastatic lesions were categorized based on six sites of involvement.

Imaging Calreticulin for Early Detection of Immunogenic Cell Death During Anticancer Treatment.

Surface-exposed calreticulin (ecto-CRT) is a well-known "eat-me" signal exhibited by dying cells that contributes to their recognition and destruction by the immune system. We assessed the use of a CRT-specific binding peptide for imaging ecto-CRT during immunogenic cell death and its utility for early prediction of treatment response. A synthetic CRT-specific peptide, KLGFFKR (CRTpep), was labeled with fluorescein isothiocyanate or F, and the characteristics of ecto-CRT were evaluated in a colon cancer cell line in vitro and in vivo.

Bisoprolol-based F-PET tracer: Synthesis and preliminary in vivo validation of β-blocker selectivity for β-adrenergic receptors in the heart.

The selectivity of a drug toward various isoforms of the target protein family is important in terms of toxicology. Typically, drug or candidate selectivity is assessed by in vitro assays, but in vivo investigations are currently lacking. Positron emission tomography (PET) allows the non-invasive determination of the in vivo distribution of a radiolabeled drug, which can provide in vivo data regarding drug selectivity.

Production of Cu-labeled monobody for imaging of human EphA2-expressing tumors.

We previously reported on the monobody E1, which specifically targets the tumor marker hEphA2. In this study, we labeled NOTA-conjugated E1 with Cu (Cu-NOTA-E1) and evaluated biologic characteristics. The uptake of Cu-NOTA-E1 in PC3 cells (a human prostate cancer cell line) with high expression of hEphA2 increased in a time-dependent manner.

Ultrasensitive detection of malignant melanoma using PET molecular imaging probes.

Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the F-labeled pyridine-based benzamide derivatives -(2-(dimethylamino)ethyl)-5-[F]fluoropicolinamide ([F]DMPY2) and -(2-(dimethylamino)ethyl)-6-[F]fluoronicotinamide ([F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task.

Imaging of tumor colonization by using F-FDS PET.

Tumor-targeting bacteria have been actively investigated as a new therapeutic tool for solid tumors. However, imaging of tumor-targeting bacteria has not been fully established. F-fluorodeoxysorbitol (FDS) positron emission tomography (PET) is known to be capable of imaging Gram-negative Enterobacteriaceae infection.

-(2-(Dimethylamino)Ethyl)-4-F-Fluorobenzamide: A Novel Molecular Probe for High-Contrast PET Imaging of Malignant Melanoma.

Malignant melanoma is an aggressive and serious form of skin cancer, with prognosis and treatment outcome depending heavily on the clinical stage of the disease at the time of diagnosis. Here, we synthesized a novel F-labeled benzamide derivative to target melanoma and then evaluated its biologic characteristics in small-animal models. -(2-(dimethylamino)ethyl)-4-F-fluorobenzamide (F-DMFB) was synthesized by reaction of -succinimidyl 4-F-fluorobenzoate with -dimethylethylenediamine.

Acetazolamide-based [F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors.

Carbonic anhydrase IX is overexpressed in many solid tumors including hypoxic tumors and is a potential target for cancer therapy and diagnosis. Reported imaging agents targeting CA-IX are successful mostly in clear cell renal carcinoma as SKRC-52 and no candidate was approved yet in clinical trials for imaging of CA-IX. To validate CA-IX as a valid target for imaging of hypoxic tumor, we designed and synthesized novel [F]-PET tracer (1) based on acetazolamide which is one of the well-known CA-IX inhibitors and performed imaging study in CA-IX expressing hypoxic tumor model as 4T1 and HT-29 in vivo models other than SKRC-52.

Cu-Labeled Repebody Molecules for Imaging of Epidermal Growth Factor Receptor-Expressing Tumors.

The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed nonantibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, 3 Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biologic characteristics were assessed in cultured cells and tumor-bearing mice.

A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors.

The accurate detection of disease-related biomarkers is crucial for the early diagnosis and management of disease in personalized medicine. Here, we present a molecular imaging of human epidermal growth factor receptor (EGFR)-expressing malignant tumors using an EGFR-specific repebody composed of leucine-rich repeat (LRR) modules. The repebody was labeled with either a fluorescent dye or radioisotope, and used for imaging of EGFR-expressing malignant tumors using an optical method and positron emission tomography.

Engineering of monobody conjugates for human EphA2-specific optical imaging.

In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E.

Isolation and Characterization of a Monobody with a Fibronectin Domain III Scaffold That Specifically Binds EphA2.

Monobodies are binding scaffold proteins originating from a human fibronectin domain III (Fn3) scaffold that can be easily engineered with specificity and affinity. Human EphA2 (hEphA2) is an early detection marker protein for various tumors including lung, breast, and colon cancer. In this study, we isolated two hEphA2-specific monobodies (E1 and E10) by screening a yeast surface display library.

In-house development of an optimized synthetic module for routine [11C]acetate production.

[11C]Acetate, a radiotracer for PET imaging, is a promising radiopharmaceutical for overcoming the limitation of 2-deoxy-2-[18F]fluoro-D-glucose in a number of cancers. Here, the optimized automatic synthesis of [11C]acetate using an in-house-developed module under different conditions has been reported for routine production. [11C]CO2 was produced in a 16.

A simple, fast, and easy assay for transition metal-catalyzed coupling reactions using a paper-based colorimetric iodide sensor.

A paper-based colorimetric iodide sensor (PBCIS) that consists of filter paper treated with starch and an oxidant is developed. It has been employed as a protocol to obtain the extent of conversion of aryl iodides in C-C, C-N, C-O and C-S bond formations, including polymer-supported Heck reactions, by transition metal catalysts such as palladium, nickel and copper.