Editorial

4 pages, 161 KiB

Open AccessEditorial

Special Issue: “Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022”

by Junbo Zhang

Pharmaceuticals 2024, 17(1), 49; https://doi.org/10.3390/ph17010049 - 28 Dec 2023

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Molecular imaging is partly defined as in vivo imaging of biological or biochemical processes using various markers [...] Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

Research

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13 pages, 2130 KiB

Open AccessArticle

Preparation and Bioevaluation of a Novel ^99mTc-Labeled Glucose Derivative Containing Cyclohexane as a Promising Tumor Imaging Agent

by Junhong Feng, Xuran Zhang, Yuhao Jiang, Qing Ruan, Qianna Wang and Junbo Zhang

Pharmaceuticals 2023, 16(4), 612; https://doi.org/10.3390/ph16040612 - 18 Apr 2023

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Abstract

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [^99mTc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without [...] Read more.

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [^99mTc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without purification, [^99mTc]Tc-CNMCHDG had a high radiochemical purity of over 95% and great in vitro stability and hydrophilicity (log P = −3.65 ± 0.10). In vitro cellular uptake studies showed that the uptake of [^99mTc]Tc-CNMCHDG was significantly inhibited by pre-treatment with _D-glucose and increased by pre-treatment with insulin. Preliminary cellular studies have demonstrated that the mechanism by which the complex enters into cells may be related to GLUTs. The results of biodistribution and SPECT imaging studies displayed high tumor uptake and good retention of [^99mTc]Tc-CNMCHDG in A549 tumor-bearing mice (4.42 ± 0.36%ID/g at 120 min post-injection). Moreover, [^99mTc]Tc-CNMCHDG exhibited excellent tumor-to-non-target ratios and a clean imaging background and is a potential candidate for clinical transformation. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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12 pages, 4214 KiB

Open AccessArticle

SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis

by Xiu Luo, Zhe Zhang, Chao Cheng, Tao Wang, Danzhou Fang, Changjing Zuo, Gengbiao Yuan, Rou Li and Xiao Li

Pharmaceuticals 2023, 16(3), 423; https://doi.org/10.3390/ph16030423 - 10 Mar 2023

Cited by 1 | Viewed by 1912

Abstract

The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, ^99mTc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared [...] Read more.

The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, ^99mTc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared with ¹⁸F-FDG or ⁶⁸Ga-FAPI-04 PET/CT. The radio-labeling rate of ^99mTc-HYNIC-FAPI-04 was greater than 90%, and the radiochemical purity was >99% after purification with sep-pak C18 column. In vitro cell uptake experiments of ^99mTc-HYNIC-FAPI-04 showed good FAP binding specificity, and the cellular uptake significantly decreased when blocked by DOTA-FAPI-04, reflecting the similar targeting mechanism of HYNIC-FAPI-04 and DOTA-FAPI-04. SPECT/CT imaging showed that U87MG tumor was distinguishable and of a high uptake of ^99mTc-HYNIC-FAPI-04 (2.67 ± 0.35 %ID/mL at 1.5 h post injection (h P.I.), while tumor signal of FAP-negative HUH-7 was as low as 0.34 ± 0.06 %ID/mL. At 5 h P.I., U87MG tumor was still distinguishable (1.81 ± 0.20 %ID/mL). In comparison, although U87MG tumor was of obvious ⁶⁸Ga-FAPI-04 uptake and clearly visible at 1 h P.I., the tumorous radioactive signals were fuzzy at 1.5 h P.I. ^99mTc-HYNIC-FAPI-04 specifically bound to FAP-positive tumors and qualified with the ability of evaluating tumor fibrosis over longer time windows. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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12 pages, 2531 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression

by Liang Xu, Lixia Zhang, Beibei Liang, Shiyu Zhu, Gaochao Lv, Ling Qiu and Jianguo Lin

Pharmaceuticals 2023, 16(2), 213; https://doi.org/10.3390/ph16020213 - 30 Jan 2023

Cited by 10 | Viewed by 1596

Abstract

Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to [...] Read more.

Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to PD-L1 expression in tumors. Therefore, accurate measurement of PD-L1 expression will help to screen cancer patients and improve the overall response rate. A small molecular positron emission tomography (PET) probe [¹⁸F]LP-F containing a biphenyl moiety was designed and synthesized for measurement of PD-L1 expression in tumors. The PET probe [¹⁸F]LP-F was obtained with a radiochemical yield of 12.72 ± 1.98%, a radiochemical purity of above 98% and molar activity of 18.8 GBq/μmol. [¹⁸F]LP-F had good stability in phosphate buffer saline (PBS) and mouse serum. In vitro assay indicated that [¹⁸F]LP-F showed moderate affinity to PD-L1. Micro-PET results showed that the tumor accumulation of [¹⁸F]LP-F in A375 tumor was inferior to that in A375-hPD-L1 tumor. All the results demonstrated that [¹⁸F]LP-F could specifically bind to PD-L1 and had a potential application in non-invasive evaluation of PD-L1 expression in tumors. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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10 pages, 2422 KiB

Open AccessArticle

⁶⁸Ga-HBED-CC-WL-12 PET in Diagnosing and Differentiating Pancreatic Cancers in Murine Models

by Qiying Xiang, Danni Li, Chao Cheng, Kai Xu and Changjing Zuo

Pharmaceuticals 2023, 16(1), 80; https://doi.org/10.3390/ph16010080 - 05 Jan 2023

Cited by 3 | Viewed by 1754

Abstract

Positron emission tomography (PET) has been proven as an important technology to detect the expression of programmed death ligand 1 (PD-L1) non-invasively and in real time. As a PD-L1 inhibitor, small peptide WL12 has shown great potential in serving as a targeting molecule [...] Read more.

Positron emission tomography (PET) has been proven as an important technology to detect the expression of programmed death ligand 1 (PD-L1) non-invasively and in real time. As a PD-L1 inhibitor, small peptide WL12 has shown great potential in serving as a targeting molecule to guide PD-L1 blockade therapy in clinic. In this study, WL12 was modified with HBED-CC to label ⁶⁸Ga in a modified procedure, and the biologic properties were evaluated in vitro and in vivo. ⁶⁸Ga-HBED-CC-WL12 showed good stability in saline and can specifically target PD-L1-positive cells U87MG and PANC02. In PANC02-bearing mice, ⁶⁸Ga-HBED-CC-WL12 showed fast permeation in subcutaneous tumors within 20 min (SUV_max 0.37) and was of higher uptake in 90 min (SUV_max 0.38). When compared with 18F-FDG, ⁶⁸Ga-FAPI-04, and ⁶⁸Ga-RGD, ⁶⁸Ga-HBED-CC-WL12 also demonstrated great image quality and advantages in evaluating immune microenvironment. This study modified the ⁶⁸Ga-labeling procedure of WL12 and obtained better biologic properties and further manifested the clinical potential of ⁶⁸Ga-HBED-CC-WL12 for PET imaging and guiding for immunotherapy. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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13 pages, 2303 KiB

Open AccessArticle

Preparation and Evaluation of ⁶⁴Cu-Radiolabled Dual-Ligand Multifunctional Gold Nanoparticles for Tumor Theragnosis

by Karim Mhanna, Wei Qian, Ziyun Zhong, Allen F. Brooks, Erika Ouchi, Jenelle Stauff, Janna Arteaga, Maria Papachristou, Ioannis E. Datseris, Bing Liu, Xia Shao and Peter J. H. Scott

Pharmaceuticals 2023, 16(1), 71; https://doi.org/10.3390/ph16010071 - 02 Jan 2023

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Abstract

Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation [...] Read more.

Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation of functional ligands onto the AuNPs can be tunable between 0% and 100% coverage. By taking advantage of this property, AuNPs functionalized by two different types of active targeting ligands with predetermined ratios were fabricated. The quantitatively controllable conjugation to construct a mixed monolayer of multiple biological molecules at a certain ratio onto the surface of AuNPs was achieved and a chelator-free ⁶⁴Cu-labeling method was developed. We report here the manufacture, radiosynthesis and bioevaluation of three different types of dual-ligand AuNPs functionalized with two distinct ligands selected from glucose, arginine–glycine–aspartate (RGD) peptide, and methotrexate (MTX) for tumor theragnosis. The preclinical evaluation demonstrated that tumor uptakes and retention of two components AuNP conjugates were higher than that of single-component AuNP conjugates. Notably, the glucose/MT- modified dual-ligand AuNP conjugates showed significant improvement in tumor uptake and retention. The novel nanoconjugates prepared in this study make it possible to integrate several modalities with a single AuNP for multimodality imaging and therapy, combining the power of chemo-, thermal- and radiation therapies together. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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12 pages, 2955 KiB

Open AccessArticle

Automatic Production of [¹⁸F]F-DOPA Using the Raytest SynChrom R&D Module

by Paweł Waśniowski, Jolanta Czuczejko, Michał Chuchra, Mateusz Wędrowski, Dawid Marciniak, Stanisław Sobiak and Bogdan Małkowski

Pharmaceuticals 2023, 16(1), 10; https://doi.org/10.3390/ph16010010 - 22 Dec 2022

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Abstract

[¹⁸F]F-DOPA is widely used in PET diagnostics. Diseases diagnosed with this tracer are schizophrenia, Parkinson’s disease, gliomas, neuroendocrine tumors, pheochromocytomas, and pancreatic adenocarcinoma. It should be noted that the [¹⁸F]F-DOPA tracer has been known for over 30 years. However, [...] Read more.

[¹⁸F]F-DOPA is widely used in PET diagnostics. Diseases diagnosed with this tracer are schizophrenia, Parkinson’s disease, gliomas, neuroendocrine tumors, pheochromocytomas, and pancreatic adenocarcinoma. It should be noted that the [¹⁸F]F-DOPA tracer has been known for over 30 years. However, the methods of radiosynthesis applied in the past did not allow its clinical use due to low efficiency and purity. Currently, in the market, one encounters different types of radiosynthesis using the fluorine ¹⁸F isotope and variants of the same method. The synthesis and its modifications were carried out using a Raytest Synchrom R&D module. The synthesis consists of the following steps: (a) binding of the fluoride anion ¹⁸F⁻ on an anion exchange column; (b) elution with TBAHCO₃⁻; (c) nucleophilic fluorination to the ABX 1336 precursor; (d) purification of the intermediate product on the C18ec column; (e) Baeyer–Villiger oxidation; (f) hydrolysis; and (gfinal purification of the crude product on a semipreparative column. The nucleophilic synthesis of [¹⁸F]F-DOPA was successfully performed in 120 min, using the ABX 1336 precursor on the Raytest SynChrom R&D module, with a radiochemical yield (RCY) of 15%, radiochemical purity (RCP) ≥ 97%, and enantiomeric purity (ee) ≥ 96%. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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15 pages, 5300 KiB

Open AccessArticle

Optimized ⁶⁸Ga-Labeled Urea-Based PSMA-Targeted PET Tracers for Prostate Cancer

by Yitian Wu, Xiaojun Zhang, Ying Zhang, Baixuan Xu, Jiahe Tian and Jinming Zhang

Pharmaceuticals 2022, 15(8), 1001; https://doi.org/10.3390/ph15081001 - 14 Aug 2022

Cited by 2 | Viewed by 1723

Abstract

Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have become some of the most promising tools for the diagnosis and therapy prostate cancer (PCa). The structure of existing PSMA-targeted PET tracers still needs to be optimized to improve their pharmacokinetic properties and tumor-to-background ratio. In this [...] Read more.

Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have become some of the most promising tools for the diagnosis and therapy prostate cancer (PCa). The structure of existing PSMA-targeted PET tracers still needs to be optimized to improve their pharmacokinetic properties and tumor-to-background ratio. In this study, we modified the structure of a well-studied PSMA tracer, and six novel tracers with variable hydrophilicity and pharmacokinetics were developed and evaluated both in vitro and in vivo. All of the novel tracers showed high hydrophilicity (log p = −2.99 ± 0.33 to −3.49 ± 0.01), rapid clearance rates (elimination half-times = 15.55 to 35.97 min), and high affinity for PSMA (Ki = 8.11 ± 0.49 to 42.40 ± 2.11 nM) in vitro. Specific cell binding and micro-PET experiments showed that [⁶⁸Ga]Ga-PSMA-Q displayed the highest specific PSMA+ cell uptake (3.75 ± 0.35 IA%/10⁶ at 60 min), tumor uptake (SUVmax = 0.97 ± 0.24 at 60 min p.i.), and tumor-to-muscle ratio (59.33 ± 5.72 at 60 min p.i.), while the tumor-to-muscle ratio was much higher than that of [⁶⁸Ga]Ga-PSMA-617. The results of this study validate the clinical potential of [⁶⁸Ga]Ga-PSMA-Q for PET imaging and further targeted therapy of prostate cancer. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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14 pages, 2561 KiB

Open AccessArticle

An Albumin-Binding PSMA Ligand with Higher Tumor Accumulation for PET Imaging of Prostate Cancer

by Ya’nan Ren, Teli Liu, Chen Liu, Xiaoyi Guo, Feng Wang, Hua Zhu and Zhi Yang

Pharmaceuticals 2022, 15(5), 513; https://doi.org/10.3390/ph15050513 - 22 Apr 2022

Cited by 4 | Viewed by 2006

Abstract

Prostate-specific membrane antigen (PSMA) is an ideal target for the diagnosis and treatment of prostate cancer. Due to the short half-life in blood, small molecules/peptides are rapidly cleared by the circulatory system. Prolonging the half-life of PSMA probes has been considered as an [...] Read more.

Prostate-specific membrane antigen (PSMA) is an ideal target for the diagnosis and treatment of prostate cancer. Due to the short half-life in blood, small molecules/peptides are rapidly cleared by the circulatory system. Prolonging the half-life of PSMA probes has been considered as an effective strategy to improve the tumor detection. Herein, we reported a ⁶⁴Cu-labeled PSMA tracer conjugating with maleimidopropionic acid (MPA), ⁶⁴Cu-PSMA-CM, which showed an excellent ability to detect PSMA-overexpressing tumors in delayed time. Cell experiments in PSMA-positive 22Rv1 cells, human serum albumin binding affinity, and micro-PET imaging studies in 22Rv1 model were performed to investigate the albumin binding capacity and PSMA specificity. Comparisons with ⁶⁴Cu-PSMA-BCH were performed to explore the influence of MPA on the biological properties. ⁶⁴Cu-PSMA-CM could be quickly prepared within 30 min. The uptake of ⁶⁴Cu-PSMA-CM in 22Rv1 cells increased over time and it could bind to HSA with a high protein binding ratio (67.8 ± 1.5%). When compared to ⁶⁴Cu-PSMA-BCH, ⁶⁴Cu-PSMA-CM demonstrated higher and prolonged accumulation in 22Rv1 tumors, contributing to high tumor-to-organ ratios. These results showed that ⁶⁴Cu-PSMA-CM was PSMA specific with a higher tumor uptake, which demonstrated that MPA is an optional strategy for improving the radioactivity concentration in PSMA-expressing tumors and for developing the ligands for PSMA radioligand therapy. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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Review

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18 pages, 968 KiB

Open AccessEditor’s ChoiceReview

Recent Advances in Hepatocellular Carcinoma Treatment with Radionuclides

by Ruiqi Liu, Hong Li, Yihua Qiu, Hongguang Liu and Zhen Cheng

Pharmaceuticals 2022, 15(11), 1339; https://doi.org/10.3390/ph15111339 - 28 Oct 2022

Cited by 2 | Viewed by 1890

Abstract

As the third leading cause of cancer death worldwide, hepatocellular carcinoma (HCC) is characterized by late detection, difficult diagnosis and treatment, rapid progression, and poor prognosis. Current treatments for liver cancer include surgical resection, radiofrequency ablation, liver transplantation, chemotherapy, external radiation therapy, and [...] Read more.

As the third leading cause of cancer death worldwide, hepatocellular carcinoma (HCC) is characterized by late detection, difficult diagnosis and treatment, rapid progression, and poor prognosis. Current treatments for liver cancer include surgical resection, radiofrequency ablation, liver transplantation, chemotherapy, external radiation therapy, and internal radionuclide therapy. Radionuclide therapy is the use of high-energy radiation emitted by radionuclides to eradicate tumor cells, thus achieving the therapeutic effect. Recently, with the continuous development of biomedical technology, the application of radionuclides in treatment of HCC has progressed steadily. This review focuses on three types of radionuclide-based treatment regimens, including transarterial radioembolization (TARE), radioactive seed implantation, and radioimmunotherapy. Their research progress and clinical applications are summarized. The advantages, limitations, and clinical potential of radionuclide treatment of HCC are discussed. Full article

(This article belongs to the Special Issue Molecular Imaging in Oncology: Radiopharmaceuticals for PET and SPECT 2022)

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