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Molecular Imaging and Treatment Monitoring of Cancer

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 24043

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Prof. Dr. Samuel Achilefu

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Guest Editor

Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Interests: cancer imaging and therapy; fluorescence lifetime; molecular imaging agents; multimodal imaging; nanomedicine; near-infrared fluorescent dyes; nuclear imaging, peptides; spectroscopy

Special Issue Information

Dear Colleagues,

The evolution of molecular imaging over the past two decades has ushered in new approaches to detect, treat, and monitor the treatment response of pathophysiologic conditions in animal models of human diseases. In particular, the application of these methods to cancer imaging and therapy holds great promise in improving the accuracy of cancer detection and the efficacy of targeted therapies, as well as reporting the functional status and state of the disease. As a result, new molecular imaging probes and methods are expected to provide diagnostic information beyond what is currently available in clinics. Thus, in addition to reporting the presence of cancer, emerging molecular imaging probes could also determine tumor viability, type, stage, heterogeneity, and potential response to treatment. The goal of this Special Issue is to assemble pertinent research papers, perspectives, and concise reviews that illustrate how molecular imaging can overcome current challenges in cancer detection, staging, and response to therapy. Manuscripts that cover the diverse molecular imaging platforms are welcome. These include optical, nuclear, ultrasonic, magnetic resonance, and multimodal imaging probes and methods. Examples of research work that have advanced from bench to bedside are also encouraged, including the challenges and opportunities in obtaining regulatory approval to use molecule probes in human patients.

Prof. Dr. Samuel Achilefu
Guest Editor

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Keywords

Cancer imaging
Imaging function status of cancer
Imaging hypoxic and metabolic state of cancer
Imaging tumor microenvironment
Magnetic resonance imaging probes and methods
Monitoring treatment response
Multimodal imaging probes and methods
Nanoparticles in cancer imaging and therapy
Nuclear imaging agents and methods
Optical imaging probes and methods
Photoacoustic imaging probes and methods
Translation of new molecular probes to clinic
Ultrasonic imaging probes and methods

Published Papers (5 papers)

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Research

12 pages, 1657 KiB

Open AccessArticle

Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging

by Maiju Soikkeli, Kaisa Horkka, Jani O. Moilanen, Marjut Timonen, Jari Kavakka and Sami Heikkinen

Molecules 2018, 23(5), 1034; https://doi.org/10.3390/molecules23051034 - 27 Apr 2018

Cited by 12 | Viewed by 4437

Abstract

Cancer is a widespread and life-threatening disease and its early-stage diagnosis is vital. One of the most effective, non-invasive tools in medical diagnostics is magnetic resonance imaging (MRI) with the aid of contrast agents. Contrast agents that are currently in clinical use contain metals, causing some restrictions in their use. Also, these contrast agents are mainly non-specific without any tissue targeting capabilities. Subsequently, the interest has notably increased in the research of organic, metal-free contrast agents. This study presents a new, stable organic radical, TEEPO-Met, where a radical moiety 2,2,6,6-tetraethylpiperidinoxide (TEEPO) is attached to an amino acid, methionine (Met), as a potentially tumour-targeting moiety. We describe the synthesis, stability assessment with electron paramagnetic resonance (EPR) spectroscopy and relaxation enhancement abilities by an in vitro nuclear magnetic resonance (NMR) and phantom MRI studies of TEEPO-Met. The new compound proved to be stable notably longer than the average imaging time in conditions mimicking a biological matrix. Also, it significantly reduced the relaxation times of water, making it a promising candidate as a novel tumour targeting contrast agent for MRI. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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10 pages, 593 KiB

Open AccessArticle

Heterogeneity of Circulating Tumor Cells in Neoadjuvant Chemotherapy of Breast Cancer

by Evgeniya V. Kaigorodova, Olga E. Savelieva, Liubov A. Tashireva, Natalia A. Tarabanovskaya, Elena I. Simolina, Evgeny V. Denisov, Elena M. Slonimskaya, Evgeny L. Choynzonov and Vladimir M. Perelmuter

Molecules 2018, 23(4), 727; https://doi.org/10.3390/molecules23040727 - 22 Mar 2018

Cited by 31 | Viewed by 4314

Abstract

The biological properties of circulating tumor cells (CTCs), and their dynamics during neoadjuvant chemotherapy are important, both for disease progression prediction and therapeutic target determination, with the aim of preventing disease progression. The aim of our study was to estimate of different CTC subsets in breast cancer during the NACT (neoadjuvant chemotherapy). The prospective study includes 27 patients with invasive breast cancer, T2-4N0-3M0, aged 32 to 60 years. Venous heparinized blood samples, taken before and after biopsy, after each courses of chemotherapy (on days 3–7), and before surgical intervention, served as the material for this study. Different subsets of circulating tumor cells were determined on the basis of the expression of EpCAM, CD45, CD44, CD24, and N-Cadherin using flow cytometry. As the result of this study, it has been observed that significant changes in the quantity of the different subsets of circulating tumor cells in patients’ blood were observed after carrying out the 3rd course of NACT. NACT causes significant changes in the quantity of six CTC subsets, with various combinations of stemness and epithelial-mesenchymal transition (EMT) properties. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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16 pages, 5502 KiB

Open AccessArticle

In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity

by Tamer M. Sakr, Mohammed A. Khedr, Hassan M. Rashed and Maged E. Mohamed

Molecules 2018, 23(2), 496; https://doi.org/10.3390/molecules23020496 - 23 Feb 2018

Cited by 25 | Viewed by 5171

Abstract

l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium (^99mTc)–phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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21 pages, 4483 KiB

Open AccessArticle

Overexpression of Receptor Tyrosine Kinase EphB4 Triggers Tumor Growth and Hypoxia in A375 Melanoma Xenografts: Insights from Multitracer Small Animal Imaging Experiments

by Christin Neuber, Birgit Belter, Sebastian Meister, Frank Hofheinz, Ralf Bergmann, Hans-Jürgen Pietzsch and Jens Pietzsch

Molecules 2018, 23(2), 444; https://doi.org/10.3390/molecules23020444 - 17 Feb 2018

Cited by 11 | Viewed by 4965

Abstract

Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor angiogenesis also in malignant melanoma. Considering the limited in vivo data available, we have conducted a systematic multitracer and multimodal imaging investigation in EphB4-overexpressing and mock-transfected A375 melanoma xenografts. Tumor growth, perfusion, and hypoxia were investigated by positron emission tomography. Vascularization was investigated by fluorescence imaging in vivo and ex vivo. The approach was completed by magnetic resonance imaging, radioluminography ex vivo, and immunohistochemical staining for blood and lymph vessel markers. Results revealed EphB4 to be a positive regulator of A375 melanoma growth, but a negative regulator of tumor vascularization. Resulting in increased hypoxia, this physiological characteristic is considered as highly unfavorable for melanoma prognosis and therapy outcome. Lymphangiogenesis, by contrast, was not influenced by EphB4 overexpression. In order to distinguish between EphB4 forward and EphrinB2, the natural EphB4 ligand, reverse signaling a specific EphB4 kinase inhibitor was applied. Blocking experiments show EphrinB2 reverse signaling rather than EphB4 forward signaling to be responsible for the observed effects. In conclusion, functional expression of EphB4 is considered a promising differentiating characteristic, preferentially determined by non-invasive in vivo imaging, which may improve personalized theranostics of malignant melanoma. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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4207 KiB

Open AccessArticle

Early Response Monitoring Following Radiation Therapy by Using [¹⁸F]FDG and [¹¹C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration

by Yi-Hsiu Chung, Cheng-Kun Tsai, Chiun-Chieh Wang, Hsi-Mu Chen, Kuan-Ying Lu, Han Chiu, Yu-Chun Lin, Tzu-Chen Yen and Gigin Lin

Molecules 2017, 22(11), 1946; https://doi.org/10.3390/molecules22111946 - 10 Nov 2017

Cited by 5 | Viewed by 4449

Abstract

We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) and [¹¹C]acetate ([¹¹C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [¹⁸F]FDG and [¹¹C]ACT PET were performed before and following irradiation (RT, 15Gy) for transgenic adenocarcinoma of mouse prostate xenografts. The underlying metabolomics alterations of tumor tissues were analyzed by using ex vivo NMR. The [¹⁸F]FDG total lesion glucose (TLG) of the tumor significant increased in the RT group at Days 1 and 3 post-irradiation, compared with the non-RT group (p < 0.05). The [¹¹C]ACT maximum standard uptake value (SUVmax) in RT (0.83 ± 0.02) and non-RT groups (0.85 ± 0.07) were not significantly different (p > 0.05). The ex vivo NMR analysis showed a 1.70-fold increase in glucose and a 1.2-fold increase in acetate in the RT group at Day 3 post-irradiation (p < 0.05). Concordantly, the expressions of cytoplasmic acetyl-CoA synthetase in the irradiated tumors was overexpressed at Day 3 post-irradiation (p < 0.05). Therefore, TLG of [¹⁸F]FDG in vivo PET images can map early treatment response following irradiation and be a promising prognostic indicator in a longitudinal preclinical study. The underlying metabolic alterations was not reflected by the [¹¹C]ACT PET. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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