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The ability to “see” has been a clinical necessity. Although the discovery of X-ray sparked the idea of seeing through and inside of our body and propelled the development of modern medicine, it was the advent of molecular imaging that has been driving the ongoing clinical shift toward individualized and precision healthcare [1, 2]. Nuclear medicine techniques, including positron emission tomography (PET) and single photon emission computed tomography (SPECT), enable us to appreciate the complex structural and molecular dynamics that play out in our bodies. The ability to see how drug molecules metabolize, to observe how biological processes progress, and to visualize how cells and organs function is an incredible leap forward in understanding human health and safeguarding it.
As our observations expand, so does our desire to understand. While [18F]FDG PET/CT has become a clinical routine to inform the status of glucose metabolism for diagnosis and staging of cancers, it was not until recently that researchers confirming tumor-recruited immune cells are the true major source of increased FDG uptake [3]. Similar cases are [68Ga]/[177Lu]-PSMA tracers for prostate cancer theranostics; recent evidence has confirmed that these tracers are also good for imaging and treatment of non-prostate cancers such as hepatocellular carcinoma by targeting angiogenesis [4, 5]. Fibroblast activating protein (FAP)-targeted agents are rapidly shaping the clinical management of various kinds of diseases, especially cancers [6, 7]. Meanwhile, massive preclinical studies are being conducted to improve the therapeutic efficacies [8,9,10]. A similar example goes with C-X-C chemokine receptor 4 (CXCR4)-targeted radiopharmaceuticals [11, 12]. These findings highlight the importance of preclinical imaging research and translational studies in updating our knowledge, guiding better diagnosis and treatment, generating personalized treatment plan, and expanding the current landscape of precision medicine.
To facilitate clearer, deeper, and better molecular imaging, interdisciplinary efforts are called upon. In response to the current shortage of specific imaging tracers, several novel nuclear imaging probes, in the forms of small molecules, peptides, oligonucleotides [13], antibodies [14,15,16], and antibody fragments, have been developed and evaluated in not only animals but also first-in-human studies. New tracers demand updated theories on “structure-effect” relationships [17], and studies regarding the choice of radionuclides, chelators, linkers, functional groups, molecular modifications, and overall drug pharmacokinetics have been another research hot spot [18]. Other than drug development to see disease lesions clearer, accurate image quantification and reconstruction have been vital in helping researchers and clinicians understand disease progress and underlying mechanisms. Traditional theory on PET and SPECT image spatial-temporal resolution and sensitivity has been challenged by modern techniques. New imaging machines, faster reconstruction algorithms, reconstruction-free PET imaging [19], and the implementation of artificial intelligence (AI) have encouraged deeper research in the fields of nuclear medicine. Total-body PET machine has awed many of us since it undoubtedly shows the potential to change clinical practice and preclinical tracer development. Very recently, scientists reported a newly developed tracing algorithm with the ability of probing one single cell on the whole-body level [20]. Another latest study shows that new imaging methods can differentiate co-administrated PET and SPECT isotopes with excellent image quality and quantification accuracy [21]. In the field of antibody theranostics [14], molecular imaging of pivotal biomarkers on the tumor cells [22, 23] and immune cells [24,25,26] broadened our understanding of the expression spectrum of those biomarkers across the body, facilitated precise evaluation of specific types of cancers, and preliminary enabled better clinical management of those diseases. Meanwhile, exquisite methods and toolbox are being developed for more facile total synthesis [27,28,29] and labeling of proteins/antibodies [30,31,32]. Along with the stride in molecular imaging, exciting progress has been made in terms of pre-targeted radioimmunotherapy [33] and targeted alpha therapy [34,35,36].
These exciting advances across various aspects of preclinical imaging and theranostics encouraged us to organize this collection on “Preclinical Molecular Imaging and Cancer Theranostics.” As we celebrate the 50th anniversary of the European Journal of Nuclear Medicine and Molecular Imaging [37], we are immensely grateful and humbled for the opportunity to host this collection, gathering opinions from researchers and clinical experts, on the latest development of molecular imaging tracers, theranostic agents, imaging technologies, and clinical translation. Despite we added the attribute “preclinical” in the title, we do welcome submissions reporting clinical evaluation of novel radiopharmaceuticals. Although clinical translation of radiopharmaceuticals should aim to solve unmet clinical demand, preclinical studies are designed to address challenges in various fields. We have carefully selected 35 research articles to include in the collection (https://link.springer.com/collections/ifdgbhigbj) and look forward to receiving exciting and inspiring work on molecular imaging and cancer theranostics enriching the collection. We genuinely believe that, through the power of molecular imaging, our ability to “see” would stand firmly in the realm of cancer theranostics and reach out toward the vast possibilities of medical exploration, on all frontiers, for all of us.
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References
James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012;92:897–965. https://doi.org/10.1152/physrev.00049.2010.
Crosby D, Bhatia S, Brindle KM, Coussens LM, Dive C, Emberton M, et al. Early detection of cancer. Science. 2022;375:eaay040. https://doi.org/10.1126/science.aay9040.
Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 2021;593:282–8. https://doi.org/10.1038/s41586-021-03442-1.
An S, Huang G, Liu J, Wei W. PSMA-targeted theranostics of solid tumors: applications beyond prostate cancers. Eur J Nucl Med Mol Imaging. 2022. https://doi.org/10.1007/s00259-022-05905-7.
Uijen MJM, Derks YHW, Merkx RIJ, Schilham MGM, Roosen J, Privé BM, et al. PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports. Eur J Nucl Med Mol Imaging. 2021;48:4350–68. https://doi.org/10.1007/s00259-021-05433-w.
Privé BM, Boussihmad MA, Timmermans B, van Gemert WA, Peters SMB, Derks YHW, et al. Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies. Eur J Nucl Med Mol Imaging. 2023. https://doi.org/10.1007/s00259-023-06144-0.
Mori Y, Dendl K, Cardinale J, Kratochwil C, Giesel FL, Haberkorn U. FAPI PET: fibroblast activation protein inhibitor use in oncologic and nononcologic disease. Radiology. 2023;220749. https://doi.org/10.1148/radiol.220749.
Millul J, Koepke L, Haridas GR, Sparrer KMJ, Mansi R, Fani M. Head-to-head comparison of different classes of FAP radioligands designed to increase tumor residence time: monomer, dimer, albumin binders, and small molecules vs peptides. Eur J Nucl Med Mol Imaging. 2023. https://doi.org/10.1007/s00259-023-06272-7.
Pang Y, Zhao L, Fang J, Chen J, Meng L, Sun L, et al. Development of FAPI tetramers to improve tumor uptake and efficacy of FAPI radioligand therapy. J Nucl Med. 2023. https://doi.org/10.2967/jnumed.123.265599.
Zhao L, Niu B, Fang J, Pang Y, Li S, Xie C, et al. Synthesis, preclinical evaluation, and a pilot clinical PET imaging study of (68)Ga-labeled FAPI dimer. J Nucl Med. 2022;63:862–8. https://doi.org/10.2967/jnumed.121.263016.
Konrad M, Rinscheid A, Wienand G, Nittbaur B, Wester H-J, Janzen T, et al. [99mTc]Tc-PentixaTec: development, extensive pre-clinical evaluation, and first human experience. Eur J Nucl Med Mol Imaging. 2023. https://doi.org/10.1007/s00259-023-06395-x.
Buck AK, Haug A, Dreher N, Lambertini A, Higuchi T, Lapa C, et al. Imaging of C-X-C motif chemokine receptor 4 expression in 690 patients with solid or hematologic neoplasms using (68)Ga-Pentixafor PET. J Nucl Med. 2022;63:1687–92. https://doi.org/10.2967/jnumed.121.263693.
Song W, Song Y, Li Q, Fan C, Lan X, Jiang D. Advances in aptamer-based nuclear imaging. Eur J Nucl Med Mol Imaging. 2022;49:2544–59. https://doi.org/10.1007/s00259-022-05782-0.
Wu Q, Yang S, Liu J, Jiang D, Wei W. Antibody theranostics in precision medicine. Med. 2023;4:69–74. https://doi.org/10.1016/j.medj.2023.01.001.
Wei W, Jiang D, Evangelista L, Cai W. Antibody-based imaging and therapy for precision medicine. Mol Pharm. 2022;19:3453–5. https://doi.org/10.1021/acs.molpharmaceut.2c00606.
Wei W, Rosenkrans ZT, Liu J, Huang G, Luo QY, Cai W. ImmunoPET: concept, design, and applications. Chem Rev. 2020;120:3787–851. https://doi.org/10.1021/acs.chemrev.9b00738.
Wang H, Liu Q, Lan X, Jiang D. Framework nucleic acids in nuclear medicine imaging: shedding light on nano-bio interactions. Angewandte Chemie (International ed in English). 2022;61:e202111980. https://doi.org/10.1002/anie.202111980.
Li M, Wang S, Kong Q, Cheng X, Yan H, Xing Y, et al. Advances in macrocyclic chelators for positron emission tomography imaging. VIEW. 2023;20230042. https://doi.org/10.1002/VIW.20230042.
Kwon SI, Ota R, Berg E, Hashimoto F, Nakajima K, Ogawa I, et al. Ultrafast timing enables reconstruction-free positron emission imaging. Nat Photonics. 2021;15:914–8. https://doi.org/10.1038/s41566-021-00871-2.
Jung KO, Kim TJ, Yu JH, Rhee S, Zhao W, Ha B, et al. Whole-body tracking of single cells via positron emission tomography. Nat Biomed Eng. 2020;4:835–44. https://doi.org/10.1038/s41551-020-0570-5.
Pratt EC, Lopez-Montes A, Volpe A, Crowley MJ, Carter LM, Mittal V, et al. Simultaneous quantitative imaging of two PET radiotracers via the detection of positron-electron annihilation and prompt gamma emissions. Nat Biomed Eng. 2023;7:1028–39. https://doi.org/10.1038/s41551-023-01060-y.
Keyaerts M, Xavier C, Heemskerk J, Devoogdt N, Everaert H, Ackaert C, et al. Phase I study of 68Ga-HER2-nanobody for PET/CT assessment of HER2 expression in breast carcinoma. J Nucl Med. 2016;57:27–33. https://doi.org/10.2967/jnumed.115.162024.
Ulaner GA, Carrasquillo JA, Riedl CC, Yeh R, Hatzoglou V, Ross DS, et al. Identification of HER2-positive metastases in patients with HER2-negative primary breast cancer by using HER2-targeted (89)Zr-Pertuzumab PET/CT. Radiology. 2020;296:370–8. https://doi.org/10.1148/radiol.2020192828.
Gondry O, Xavier C, Raes L, Heemskerk J, Devoogdt N, Everaert H, et al. Phase I study of [68Ga]Ga-Anti-CD206-sdAb for PET/CT assessment of protumorigenic macrophage presence in solid tumors (MMR phase I). J Nucl Med. 2023. https://doi.org/10.2967/jnumed.122.264853.
Farwell MD, Gamache RF, Babazada H, Hellmann MD, Harding JJ, Korn R, et al. CD8-targeted PET imaging of tumor-infiltrating T cells in patients with cancer: a phase I first-in-humans study of (89)Zr-Df-IAB22M2C, a radiolabeled anti-CD8 minibody. J Nucl Med. 2022;63:720–6. https://doi.org/10.2967/jnumed.121.262485.
Stutvoet TS, van der Veen EL, Kol A, Antunes IF, de Vries EFJ, Hospers GAP, et al. Molecular imaging of PD-L1 expression and dynamics with the adnectin-based PET tracer (18)F-BMS-986192. J Nucl Med. 2020;61:1839–44. https://doi.org/10.2967/jnumed.119.241364.
Praetorius F, Leung PJY, Tessmer MH, Broerman A, Demakis C, Dishman AF, et al. Design of stimulus-responsive two-state hinge proteins. Science. 2023;381:754–60. https://doi.org/10.1126/science.adg7731.
Huppelschoten Y, Elhebieshy A, Hameed D, Sapmaz A, Buchardt J, Nielsen T, et al. Total chemical synthesis of a functionalized GFP nanobody. ChemBioChem. 2022. https://doi.org/10.1002/cbic.202200304.
Hartmann L, Botzanowski T, Galibert M, Jullian M, Chabrol E, Zeder-Lutz G, et al. VHH characterization. Comparison of recombinant with chemically synthesized anti-HER2 VHH. Protein Sci. 2019;28:1865–79. https://doi.org/10.1002/pro.3712.
Noncanonical amino acids as doubly bio-orthogonal handles for one-pot preparation of protein multiconjugates. Nat Commun. 2023;14. https://doi.org/10.1038/s41467-023-36658-y.
Klauser PC, Chopra S, Cao L, Bobba KN, Yu B, Seo Y, et al. Covalent proteins as targeted radionuclide therapies enhance antitumor effects. ACS Cent Sci. 2023;9:1241–51. https://doi.org/10.1021/acscentsci.3c00288.
Yang E, Liu Q, Huang G, Liu J, Wei W. Engineering nanobodies for next-generation molecular imaging. Drug Discov Today. 2022;27:1622–38. https://doi.org/10.1016/j.drudis.2022.03.013.
Cheal SM, Chung SK, Vaughn BA, Cheung NV, Larson SM. Pretargeting: a path forward for radioimmunotherapy. J Nucl Med. 2022;63:1302–15. https://doi.org/10.2967/jnumed.121.262186.
Feng Y, Meshaw R, Zhao XG, Jannetti S, Vaidyanathan G, Zalutsky MR. Effective treatment of human breast carcinoma xenografts with single-dose (211)At-labeled Anti-HER2 single-domain antibody fragment. J Nucl Med. 2023;64:124–30. https://doi.org/10.2967/jnumed.122.264071.
Abou DS, Longtine M, Fears A, Benabdallah N, Unnerstall R, Johnston H, et al. Evaluation of candidate theranostics for (227)Th/(89)Zr paired radioimmunotherapy of lymphoma. J Nucl Med. 2023;64:1062–8. https://doi.org/10.2967/jnumed.122.264979.
Bidkar AP, Wang S, Bobba KN, Chan E, Bidlingmaier S, Egusa EA, et al. Treatment of prostate cancer with CD46-targeted 225Ac alpha particle radioimmunotherapy. Clin Cancer Res. 2023;29:1916–28. https://doi.org/10.1158/1078-0432.Ccr-22-3291.
Ell P. 50 years EJNM and EJNMMI. Eur J Nucl Med Mol Imaging. 2023. https://doi.org/10.1007/s00259-023-06361-7.
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Jiang, D., Wei, W. Molecular imaging for better theranostics. Eur J Nucl Med Mol Imaging 50, 3799–3801 (2023). https://doi.org/10.1007/s00259-023-06415-w
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DOI: https://doi.org/10.1007/s00259-023-06415-w