Abstract
The armamentarium of approved radiopharmaceuticals for either diagnosis or therapy is at the core of the clinical practice of today’s nuclear medicine. Nevertheless, both because the currently approved agents do not meet all the clinical needs for radionuclide targeting and because advancing knowledge in the pathophysiology of tissues/organs open in turn new opportunities, investigations continue at the preclinical and clinical validation level for the development of new radiopharmaceuticals, most of which are not approved yet for commercial use. Concerning in particular the diagnostic applications of nuclear medicine to oncology, ongoing investigations in the search for tumor-targeting agents with better specificity and sensitivity are countless, possibly within the scenario of theranostics – that is, with the dual potential for imaging and for therapy, depending on the specific radionuclide employed for radiolabeling. We will focus this chapter on the most promising imaging agents labeled with single-photon-emitting radionuclides based on some of the mechanisms that are typical for tumor cells/tissues.
Keywords
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- BTAP:
-
Bis(thioacetamido)pentanoyl
- DOTA:
-
2-(4-Isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (macrocyclic coupling agent to label compounds of biological interest with metal radionuclides)
- DTPA:
-
Diethylenetriaminepentaacetic acid
- EGF:
-
Epidermal growth factor
- EGFR:
-
Epidermal growth factor receptor
- FDA:
-
United States Food and Drug Administration
- GMP:
-
Good manufacturing practice
- HER:
-
Human epidermal growth factor receptor
- HPLC:
-
High-performance liquid chromatography (formerly known as high-pressure liquid chromatography)
- HYNIC:
-
6-Hydrazinopyridine-3-carboxylic acid, also known as hydrazidonicotinic acid/hydrazinonicotinamide (a chelating agent)
- MMP:
-
Metalloproteinases, a family of matrix enzymes
- MRI:
-
Magnetic resonance imaging
- NIRF:
-
Near-infrared fluorescence
- PET:
-
Positron emission tomography
- RGD:
-
Tripeptide composed of L-arginine, glycine, and L-aspartic acid (a sequence that is a common element in cellular recognition)
- SPECT:
-
Single-photon emission tomography
- TGF:
-
Transforming growth factor
- TKI:
-
Tyrosine kinase inhibitor
- TPPTS:
-
3,3,3”-Phosphanetriyltris(benzenesulfonic acid) trisodium salt, a ligand also known as sodium triphenylphosphine trisulfonate
- VEGF:
-
Vascular endothelial growth factor
References
Ravdin P. The use of HER2 testing in the management of breast cancer. Semin Oncol. 2000;27 Suppl 9:33–42.
Roses AD. Pharmacogenetics and the practice of medicine. Nature. 2000;405(6788):857–65.
Cornelissen B. Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes. J Label Compd Radiopharm. 2014;57:310–6.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
Cavallo F, De Giovanni C, Nanni P, Forni G, Lollini PL. The immune hallmarks of cancer. Cancer Immunol Immunother. 2011;60:319–26.
James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012;92:897–965.
Mariani G, Bruselli L, Duatti A. Is PET always an advantage versus planar and SPECT? Eur J Nucl Med Mol Imaging. 2008;35:1560–5.
Pauwels EKJ, Bergstrom K, Mariani G, Kairemo K. Microdosing, imaging biomarkers and SPECT: a multi-sided tripod to accelerate drug development. Curr Pharm Des. 2009;15:928–34.
Mariani G, Strauss HW. Positron emission and single-photon emission imaging: synergy rather than competition. Eur J Nucl Med Mol Imaging. 2011;38:1189–90.
Vaupel P. Pathophysiology of solid tumors. In: Molls M, Vaupel P, Nieder C, Anscher MS, editors. The impact of tumor biology on cancer treatment and multidisciplinary strategies. Heidelberg: Springer; 2009. p. 51–92.
Bredow S, Lewin M, Hofmann B, Marecos E, Weissleder R. Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin. Eur J Cancer. 2000;36:675–81.
Zhou Y, Chakraborty S, Liu S. Radiolabeled cyclic RGD peptides as radiotracers for imaging tumors and thrombosis by SPECT. Theranostics. 2011;1:58–82.
Tsiapa I, Loudos G, Varvarigou A, Fragogeorgi E, Psimadas D, Tsotakos T, et al. Biological evaluation of an ornithine-modified 99mTc-labeled RGD peptide as an angiogenesis imaging agent. Nucl Med Biol. 2013;40:262–72.
Kimura S, Umeda IO, Moriyama N, Fujii H. Synthesis and evaluation of a novel 99mTc-labeled bioreductive probe for tumor hypoxia imaging. Bioorg Med Chem Lett. 2011;21:7359–62.
Umeda IO, Tani K, Tsuda K, Kobayashi M, Ogata M, Kimura S, et al. High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging. Ann Nucl Med. 2012;26:67–76.
Weerakkody D, Moshnikova A, Thakur MS, Moshnikova V, Daniels J, Engelman DM, et al. Family of pH (low) insertion peptides for tumor targeting. Proc Natl Acad Sci U S A. 2013;110:5834–9.
von Forstner C, Zuhayra M, Ammerpohl O, Zhao Y, Tiwari S, Jansen O, et al. Expression of L amino acid transport system 1 and analysis of iodine-123-methyltyrosine tumor uptake in a pancreatic xenotransplantation model using fused high-resolutionmicro-SPECT-MRI. Hepatobiliary Pancreat Dis Int. 2011;10:30–7.
Kondo N, Temma T, Shimizu Y, Watanabe H, Higano K, Takagi Y, et al. Miniaturized antibodies for imaging membrane type-1 matrix metalloproteinase in cancers. Cancer Sci. 2013;104:495–501.
LeBeau AM, Duriseti S, Murphy ST, Pepin F, Hann B, Gray JW, et al. Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer. Cancer Res. 2013;73:2070–81.
Cai J, Li F. Single-photon emission computed tomography tracers for predicting and monitoring cancer therapy. Curr Pharm Biotechnol. 2013;14:693–707.
Schottelius M, Wester HJ. Molecular imaging targeting peptide receptors. Methods. 2009;48:161–77.
Heskamp S, van Laarhoven HW, Molkenboer-Kuenen JD, Bouwman WH, van der Graaf WT, Oyen WJ, et al. Optimization of IGF-1R SPECT/CT imaging using 111In-labeled F(ab′)2 and Fab fragments of the monoclonal antibody R1507. Mol Pharm. 2012;9:2314–21.
Muller C. Folate based radiopharmaceuticals for imaging and therapy of cancer and inflammation. Curr Pharm Des. 2012;18:1058–83.
Kassis AI, Adelstein SJ, Mariani G. Radiolabeled nucleoside analogs in cancer diagnosis and therapy. Q J Nucl Med. 1996;40:301–19.
Mariani G, Bodei L, Adelstein SJ, Kassis AI. Emerging roles for radiometabolic therapy of tumors based on Auger electron emission. J Nucl Med. 2000;41:1519–21.
Adelstein SJ, Kassis AI, Bodei L, Mariani G. Radiotoxicity of iodine-125 and other Auger-electron emitting radionuclides: background to therapy. Cancer Biother Radio-Pharm. 2003;18:301–16.
Bodei L, Kassis AI, Adelstein SJ, Mariani G. Radionuclide therapy with iodine-125 and other Auger-electron-emitting radionuclides: experimental models and clinical applications. Cancer Biother Radiopharm. 2003;18:861–77.
Aloj L, Aurilio M, Rinaldi V, D’Ambrosio L, Tesauro D, Peitl PK, et al. Comparison of the binding and internalization properties of 12 DOTA-coupled and 111In-labelled CCK2/gastrin receptor binding peptides: a collaborative project under COST Action BM0607. Eur J Nucl Med Mol Imaging. 2011;38:1417–25.
Forrer F, Valkema R, Bernard B, Schramm NU, Hoppin JW, Rolleman E, et al. In vivo radionuclide uptake quantification using a multi-pinhole SPECT system to predict renal function in small animals. Eur J Nucl Med Mol Imaging. 2006;33:1214–7.
Behr TM, Béhé M, Becker W. Diagnostic applications of radiolabeled peptides in nuclear endocrinology. Q J Nucl Med. 1999;43:268–80.
Behr TM, Béhé MP. Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies. Semin Nucl Med. 2002;32:97–109.
Quinn T, Zhang X, Miao Y. Targeted melanoma imaging and therapy with radiolabeled alpha-melanocyte stimulating hormone peptide analogues. G Ital Dermatol Venereol. 2010;145:245–58.
Ambrosini V, Fani M, Fanti S, Forrer F, Maecke HR. Radiopeptide imaging and therapy in Europe. J Nucl Med. 2011;52:42S–55.
Graham MM, Menda Y. Radiopeptide imaging and therapy in the United States. J Nucl Med. 2011;52:56S–63.
Tang B, Yong X, Xie R, Li QW, Yang SM. Vasoactive intestinal peptide receptor-based imaging and treatment of tumors. Int J Oncol. 2014;44:1023–31.
Hubalewska-Dydejczyk A, Sowa-Staszczak A, Tomaszuk M, Stefańska A. GLP-1 and exendin-4 for imaging endocrine pancreas. A review. Labelled glucagon-like peptide-1 analogues: past, present and future. Q J Nucl Med Mol Imaging. 2015;59:152–60.
Yang MY, Chuang H, Chen RF, Yang KD. Reversible phosphatidylserine expression on blood granulocytes related to membrane perturbation but not DNA strand breaks. J Leukoc Biol. 2002;71:231–7.
Bouter A, Carmeille R, Gounou C, Bouvet F, Degrelle SA, Evain-Brion D, et al. Review: annexin-A5 and cell membrane repair. Placenta. 2015;36 Suppl 1:S43–9.
Gottlieb RA. Part III: molecular and cellular hematology apoptosis. In: Lichtman MA, Beutler E, Kipps TJ, editors. Williams’ hematology. 7th ed. New York: McGraw-Hill Book; 2007. p. 125–30.
Ogawa K, Aoki M. Radiolabeled apoptosis imaging agents for early detection of response to therapy. Sci World J. 2014;2014:732603. doi:10.1155/2014/732603. Epub 2014 Oct 14.
Blankenberg FG. In vivo detection of apoptosis. J Nucl Med. 2008;49 Suppl 2:81S–95.
Kemerink GJ, Liu X, Kieffer D, Ceyssens S, Mortelmans L, Verbruggen AM, et al. Safety, biodistribution, and dosimetry of 99mTc-HYNIC-annexin V, a novel human recombinant annexin V for human application. J Nucl Med. 2003;44:947–52.
Tait JF, Smith C, Blankenberg FG. Structural requirements for in vivo detection of cell death with 99mTc-annexin V. J Nucl Med. 2005;46:807–15.
Belhocine T, Steinmetz N, Hustinx R, Bartsch P, Jerusalem G, Seidel L, et al. Increased uptake of the apoptosis-imaging agent 99mTc recombinant human annexin v in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res. 2002;8:2766–74.
Schaper FLWVJ, Reutelingsperger CP. 99mTc-HYNIC-annexin A5 in oncology: evaluating efficacy of anti-cancer therapies. Cancers. 2013;5:550–68.
Vangestel C, Peeters M, Mees G, Oltenfreiter R, Boersma HH, Elsinga PH, et al. In vivo imaging of apoptosis in oncology: an update. Mol Imaging. 2011;10:340–58.
Vangestel C, Van de Wiele C, Van Damme N, Staelens S, Pauwels P, Reutelingsperger CP, Peeters M. 99mTc-(CO)3 His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. J Nucl Med. 2011;52:1786–94.
Lahorte CM, van de Wiele C, Bacher K, van den Bossche B, Thierens H, van Belle S, et al. Biodistribution and dosimetry study of 123I-rh-annexin v in mice and humans. Nucl Med Commun. 2003;24:871–80.
Marconescu A, Thorpe PE. Coincident exposure of phosphatidylethanolamine and anionic phospholipids on the surface of irradiated cells. Biochim Biophys Acta. 1778;2008:2217–24.
Bevers EM, Comfurius P, Dekkers DWC, Zwaal RFA. Lipid translocation across the plasma membrane of mammalian cells. Biochim Biophys Acta. 1999;439:317–30.
Alberts B, Johnson A, Lewis J, et al. Molecular biology of the cell. 4th ed. New York: Garland Science; 2002.
Spector AA, Yorek MA. Membrane lipid composition and cellular function. J Lipid Res. 1985;26:1015–35.
Emoto K, Toyama-Sorimachi N, Karasuyama H, Inoue K, Umeda M. Exposure of phosphatidylethanolamine on the surface of apoptotic cells. Exp Cell Res. 1997;232:430–4.
Umeda M, Emoto K. Membrane phospholipid dynamics during cytokinesis: regulation of actin filament assembly by redistribution of membrane surface phospholipid. Chem Phys Lipids. 1999;101:81–91.
Mills JC, Stone NL, Erhardt J, et al. Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation. J Cell Biol. 1998;140:627–36.
Hayashi F, Nagashima K, Terui Y, et al. The structure of PA48009: the revised structure of duramycin. J Antibiot (Tokyo). 1990;43:1421–30.
Zimmermann N, Freund S, Fredenhagen A, et al. Solution structures of the lantibiotics duramycin B and C. Eur J Biochem. 1993;216:419–28.
Aoki Y, Uenaka T, Aoki J, et al. A novel peptide probe for studying the transbilayer movement of phosphatidylethanolamine. J Biochem. 1994;116:291–7.
Machaidze G, Ziegler A, Seelig J. Specific binding of Ro 09-0198 (cinnamycin) to phosphatidylethanolamine: a thermodynamic analysis. Biochemistry. 2002;41:1965–71.
Guder A, Wiedemann I, Sahl HG. Posttranslationally modified bacteriocins: the lantibiotics. Biopolymers. 2000;55:62–73.
Hosoda K, Ohya M, Kohno T, et al. Structure determination of an immunopotentiator peptide, cinnamycin, complexed with lysophosphatidylethanolamine by 1H-NMR1. J Biochem. 1996;119:226–30.
Kaletta C, Entian KD, Jung G. Prepeptide sequence of cinnamycin (Ro 09-0198): the first structural gene of a duramycin-type lantibiotic. Eur J Biochem. 1991;199:411–5.
Marki F, Hanni E, Fredenhagen A, et al. Mode of action of the lanthioninecontaining peptide antibiotics duramycin, duramycin B and C, and cinnamycin as indirect inhibitors of phospholipase A2. Biochem Pharmacol. 1991;42:2027–35.
Iwamoto K, Hayakawa T, Murate M, et al. Curvature-dependent recognition of ethanolamine phospholipids by duramycin and cinnamycin. Biophys J. 2007;93:1608–19.
Seelig J. Thermodynamics of lipid-peptide interactions. Biochim Biophys Acta. 1666;2004:40–50.
Zhao M, Li Z, Bugenhagen S. 99mTc-labeled duramycin as a novel phosphatidylethanolamine-binding molecular probe. J Nucl Med. 2008;49:1345–52.
Zhao M, Li Z. A single-step kit formulation for the 99mTc-labeling of HYNIC-Duramycin. Nucl Med Biol. 2012;39:1006–11.
Audi S, Li Z, Capacete J, Liu Y, Fang W, Shu LG, Zhao M. Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent 99mTc-Duramycin. Nucl Med Biol. 2012;39:821–5.
Wang L, Wang F, Fang W, et al. The feasibility of imaging myocardial ischemic/reperfusion injury using 99mTc-labeled duramycin in a porcine model. Nucl Med Biol. 2015;42:198–204.
Zhang Y, Stevenson GD, Barber C, et al. Imaging of rat cerebral ischemia-reperfusion injury using 99mTc-labeled duramycin. Nucl Med Biol. 2013;40:80–8.
Clough AV, Audi SH, Haworth ST, Roerig DL. Differential lung uptake of 99mTc-hexamethylpropyleneamine oxime and 99mTc-duramycin in the chronic hyperoxia rat model. J Nucl Med. 2012;53:1984–91.
Audi SH, Jacobs ER, Zhao M, Roerig DL, Haworth ST, Clough AV. In vivo detection of hyperoxia-induced pulmonary endothelial cell death using 99mTc-duramycin. Nucl Med Biol. 2015;42:46–52.
Medhora MM, Haworth S, Liu Y, Narayanan J, Gao F, Zhao M, et al. Biomarkers for radiation pneumonitis using non-invasive molecular imaging. J Nucl Med. 2016;57:1296–301.
Johnson SE, Li Z, Liu Y, Moulder JE, Zhao M. Whole-body imaging of high-dose ionizing irradiation-induced tissue injuries using 99mTc-duramycin. J Nucl Med. 2013;54:1397–403.
Elvas F, Vangestel C, Rapic S, Verhaeghe J, Gray B, Pak K, et al. Characterization of [99mTc]duramycin as a SPECT imaging agent for early assessment of tumor apoptosis. Mol Imaging Biol. 2015;17:838–47.
Luo R, Niu L, Qiu F, Fang W, Fu T, Zhao M, et al. Monitoring apoptosis of breast cancer xenograft after paclitaxel treatment with 99mTc-labeled duramycin SPECT/CT. Mol Imaging. 2016;29:15. doi:10.1177/1536012115624918.
Elvas F, Boddaert J, Vengestel C, Pak K, Gray B, Kumar-Singh S, et al. 99mTc-Duramycin SPECT imaging of early tumor response to targeted therapy: a comparison with 18F-FDG PET. J Nucl Med. 2017;58:665–70.
Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science. 1987;238:491–7.
Sivolapenko GB, Skarlos D, Pectasides D, Stathopoulou E, Milonakis A, Sirmalis G, et al. Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide. Eur J Nucl Med. 1998;25:1383–9.
Hua J, Dobrucki LW, Sadeghi MM, Zhang J, Bourke BN, Cavaliere P, et al. Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at alphavbeta3 integrin after murine hindlimb ischemia. Circulation. 2005;111:3255–60.
Bach-Gansmo T, Danielsson R, Saracco A, Wilczek B, Bogsrud TV, Fangberget A, et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692. J Nucl Med. 2006;47:1434–9.
Bach-Gansmo T, Bogsrud TV, Skretting A. Integrin scintimammography using a dedicated breast imaging, solid-state gamma-camera and 99mTc-labelled NC100692. Clin Physiol Funct Imaging. 2008;28:235–9.
Axelsson R, Bach-Gansmo T, Castell-Conesa J, McParland BJ, Study Group. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alphav beta3-selective angiogenesis imaging agent 99mTc-NC100692. Acta Radiol. 2010;51:40–6.
Dearling JL, Barnes JW, Panigrahy D, Zimmerman RE, Fahey F, Treves ST, et al. Specific uptake of 99mTc-NC100692, an αvβ3-targeted imaging probe, in subcutaneous and orthotopic tumors. Nucl Med Biol. 2013;40:788–94.
Shi J, Wang L, Kim YS, et al. Improving tumor uptake and excretion kinetics of 99mTc-labeled cyclic arginine-glycine-aspartic (RGD) dimmers with triglycine linkers. J Med Chem. 2008;51:7980–90.
Liu Z, Jia B, Shi J, et al. Tumor uptake of the RGD dimeric probe 99mTc-G3-2P4-RGD2 is correlated with integrin αVβ3 expressed on both tumor cells and neovasculature. Bioconjug Chem. 2010;21:548–55.
Zhou Y, Kim YS, Chakraborty S, Shi J, Gao H, Liu S. 99mTc-labeled cyclic RGD peptides for noninvasive monitoring of tumor integrin αVβ3 expression. Mol Imaging. 2011;10:386–97.
Ma Q, Ji B, Jia B, et al. Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy. Eur J Nucl Med Mol Imaging. 2011;38:2145–52.
Liu L, Song Y, Gao S, Ji T, Zhang H, Ji B, et al. 99mTc-3PRGD2 scintimammography in palpable and nonpalpable breast lesions. Mol Imaging. 2014;13:1–7. doi:10.2310/7290.2014.00010.
Zhu Z, Miao W, Li Q, Dai H, Ma Q, Wang F, et al. 99mTc-3PRGD2 for integrin receptor imaging of lung cancer: a multicenter study. J Nucl Med. 2012;53:716–22.
Zhao D, Jin X, Li F, Liang J, Lin Y. Integrin αvβ3 imaging of radioactive iodine-refractory thyroid cancer using 99mTc-3PRGD2. J Nucl Med. 2012;53:1872–7.
Miao W, Zheng S, Dai H, Wang F, Jin X, Zhu Z, Jia B. Comparison of 99mTc-3PRGD2 integrin receptor imaging with 99mTc-MDP bone scan in diagnosis of bone metastasis in patients with lung cancer: a multicenter study. PLoS One. 2014;9(10):e111221.
Ji S, Zhou Y, Voorbach MJ, Shao G, Zhang Y, Fox GB, et al. Monitoring tumor response to linifanib therapy with SPECT/CT using the integrin αvβ3-targeted radiotracer 99mTc-3P-RGD2. J Pharmacol Exp Ther. 2013;346:251–8.
Liu Z, Huang J, Dong C, et al. 99mTc-labeled RGD-BBN peptide for small-animal SPET/CT of lung carcinoma. Mol Pharm. 2012;9:1409–17.
Chen Q, Ma Q, Chen M, et al. An exploratory study on 99mTc-RGDBBN. Peptide scintimammography in the assessment of breast malignant lesions compared to 99mTc-3P4-RGD2. PLoS One. 2015;10(4):e0123401.
Ji T, Sun Y, Chen B, Ji B, Gao S, Ma Q, et al. The diagnostic role of 99mTc-dual receptor targeted probe and targeted peptide bombesin (RGD-BBN) SPET/CT in the detection of malignant and benign breast tumors and axillary lymph nodes compared to ultrasound. Hell J Nucl Med. 2015;18:108–13.
Bunschoten A, van Willigen DM, Buckle T, van den Berg NS, Welling MM, Spa SJ, Wester HJ, et al. Tailoring fluorescent dyes to optimize a hybrid RGD-tracer. Bioconjug Chem. 2016;27:1253–8.
Castellani P, Viale G, Dorcaratto A, Nicolò G, Kaczmarek J, Querze G, Zardi L. The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis. Int J Cancer. 1994;59:612–8.
Pini A, Viti F, Santucci A, Carnemolla B, Zardi L, Neri P, Neri D. Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two-dimensional gel. J Biol Chem. 1998;273:21769–76.
Tarli L, Balza E, Viti F, Borsi L, Castellani P, Berndorff D, Dinkelborg L, Neri D, Zardi L. A high-affinity human antibody that targets tumoral blood vessels. Blood. 1999;94:192–8.
Berndorff D, Borkowski S, Moosmayer D, Viti F, Muller-Tiemann B, Sieger S, et al. Imaging of tumor angiogenesis using 99mTc-labeled human recombinant anti-ED-B fibronectin antibody fragments. J Nucl Med. 2006;47:1707–16.
Kaczmarek J, Castellani P, Nicolò G, Spina B, Allemanni G, Zardi L. Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues. Int J Cancer. 1994;59:11–6.
Pujuguet P, Hammann A, Moutet M, Samuel JL, Martin F, Martin M. Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts. Am J Pathol. 1996;148:579–92.
Santimaria M, Moscatelli G, Viale GL, Giovannoni L, Neri G, Viti F, et al. Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. Clin Cancer Res. 2003;9:571–9.
Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997;74:111–22.
Foda HD, Zucker S. Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis. Drug Discov Today. 2001;6:478–82.
Matusiak N, van Waarde A, Bischoff R, Oltenfreiter R, van de Wiele C, Dierckx RA, et al. Probes for non-invasive matrix metalloproteinase-targeted imaging with PET and SPECT. Curr Pharm Des. 2013;19:4647–72.
Sihver W, Pietzsch J, Krause M, Baumann M, Steinbach J, Pietzsch HJ. Radiolabeled cetuximab conjugates for EGFR targeted cancer diagnostics and therapy. Pharmaceuticals (Basel). 2014;7:311–38.
Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19:183–232.
Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004;11:689–708.
Schechter NR, Yang DJ, Azhdarinia A, Kohanim S, Wendt R, Oh CS, et al. Assessment of epidermal growth factor receptor with 99mTc-ethylenedicysteine-C225 monoclonal antibody. Anticancer Drugs. 2003;14:49–56.
Schechter NR, Wendt RE, Yang DJ, Azhdarinia A, Erwin WD, Stachowiak AM, et al. Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck. J Nucl Med. 2004;45:1683–7.
Price EW, Zeglis BM, Cawthray JF, Ramogida CF, Ramos N, Lewis JS, et al. H4octapa-trastuzumab: versatile acyclic chelate system for 111In and 177Lu imaging and therapy. J Am Chem Soc. 2013;135:12707–21.
Razumienko EJ, Scollard DA, Reilly RM. Small-animal SPECT/CT of HER2 and HER3 expression in tumor xenografts in athymic mice using trastuzumab Fab-heregulin bispecific radioimmunoconjugates. J Nucl Med. 2012;53:1943–50.
Divgi CR, Welt S, Kris M, Real FX, Yeh SD, Gralla R, et al. Phase I and imaging trial of indium-111 labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J Natl Cancer Inst. 1991;83:97–104.
Lam K, Scollard DA, Chan C, Levine MN, Reilly RM. Kit for the preparation of 111In-labeled pertuzumab injection for imaging response of HER2-positive breast cancer to trastuzumab (Herceptin). Appl Radiat Isot. 2014;95:135–42.
McLarty K, Cornelissen B, Cai Z, Scollard DA, Costantini DL, Done SJ, Reilly RM. Micro-SPECT/CT with 111In-DTPA-pertuzumab sensitively detects trastuzumab-mediated HER2 downregulation and tumor response in athymic mice bearing MDA-MB-361 human breast cancer xenografts. J Nucl Med. 2009;50:1340–8.
Müller C, Mindt TL, de Jong M, Schibli R. Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy. Eur J Nucl Med Mol Imaging. 2009;36:938–46.
Müller C, Forrer F, Schibli R, Krenning EP, de Jong M. SPECT study of folate receptor-positive malignant and normal tissues in mice using a novel 99mTc-radiofolate. J Nucl Med. 2008;49:310–07.
Reber J, Struthers H, Betzel T, Hohn A, Schibli R, Müller C. Radioiodinated folic acid conjugates: evaluation of a valuable concept to improve tumor-to-background contrast. Mol Pharm. 2012;9:1213–21.
Maurer AH, Elsinga P, Fanti S, Nguyen B, Oyen WJ, Weber WA. Imaging the folate receptor on cancer cells with 99mTc-etarfolatide: properties, clinical use, and future potential of folate receptor imaging. J Nucl Med. 2014;55:701–4.
Morris RT, Joyrich RN, Naumann RW, Shah NP, Maurer AH, Strauss HW, et al. Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide). Ann Oncol. 2014;25:852–8.
Yamada Y, Nakatani H, Yanaihara H, Omote M. Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults. Ann Nucl Med. 2015;29:792–8.
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Orsini, F., Guidoccio, F., Puta, E., Mariani, G. (2017). Novel Single-Photon-Emitting Radiopharmaceuticals for Diagnostic Applications. In: Strauss, H., Mariani, G., Volterrani, D., Larson, S. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-26236-9_3
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DOI: https://doi.org/10.1007/978-3-319-26236-9_3
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Publisher Name: Springer, Cham
Print ISBN: 978-3-319-26234-5
Online ISBN: 978-3-319-26236-9
eBook Packages: MedicineReference Module Medicine