Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle

References

• Restifo NP, Smyth MJ, Snyder A. Acquired resistance to immunotherapy and future challenges. Nat Rev Cancer. 2016 ;16(2):121–126. Nature Publishing Group.
   PubMed Web of Science ®Google Scholar
• Middendorp M, Grünwald F. Update on recent developments in the therapy of differentiated thyroid cancer. Semin Nucl Med. 2010 ;40(2):145–152. Elsevier Inc.
   PubMed Web of Science ®Google Scholar
• Henriksen G, Fisher DR, Roeske JC, et al. Targeting of osseous sites with alpha-emitting 223Ra: comparison with the beta-emitter 89Sr in mice. J Nucl Med. 2003;44(2):252–259.
   PubMed Web of Science ®Google Scholar
• Van Dodewaard-de Jong J, Oprea-Lager D, Hooft L, et al. Radiopharmaceuticals for palliation of bone pain in patients with castration-resistant prostate cancer metastatic to bone: a systematic review. Eur Urol. 2015. European Association of Urology.
   Google Scholar
• Kwekkeboom DJ, Mueller-Brand J, Paganelli G, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46(1):62S– 6S.
   PubMed Web of Science ®Google Scholar
• Valkema R, Pauwels S, Kvols L, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med. 2006;36(2):147–156.
   PubMed Web of Science ®Google Scholar
• De Jong M, Valkema R, Jamar F, et al. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med. 2002;32(2):133–140.
   PubMed Web of Science ®Google Scholar
• Koppe MJ, Postema EJ, Aarts F, et al. Antibody-guided radiation therapy of cancer. Cancer Metastasis Rev. 2005;24(4):539–567.
   PubMed Web of Science ®Google Scholar
• Ghobrial I, Witzig T. Radioimmunotherapy: a new treatment modality for B-cell non-Hodgkin’s Lymphoma. Oncology (Williston Park). 2004;18(3):623–630.
   PubMed Web of Science ®Google Scholar
• Chamarthy MR, Williams SC, Moadel RM. Radioimmunotherapy of non-Hodgkin’s lymphoma: from the “magic bullets” to “radioactive magic bullets. Yale J Biol Med. 2011;84(4):391–407.
   PubMedGoogle Scholar
• Volkert WA, Goeckleler WF, Ehrhardt GJ, et al. Therapeutic radionuclides: production and decay property considerations. J Nucl Med. 1991;32(1):174–185.
   PubMed Web of Science ®Google Scholar
• Pouget JP, Navarro-Teulon I, Bardiès M, et al. Clinical radioimmunotherapy-the role of radiobiology. Nat Rev Clin Oncol. 2011;8(12):720–734.
   PubMed Web of Science ®Google Scholar
• Buchegger F, Perillo-Adamer F, Dupertuis YM, et al. Auger radiation targeted into DNA: a therapy perspective. Eur J Nucl Med Mol Imaging. 2006;33(11):1352–1363.
   PubMed Web of Science ®Google Scholar
• Mulford DA, Scheinberg DA, Jurcic JG. The promise of targeted α-particle therapy. J Nucl Med. 2005;46:199–205.
   PubMed Web of Science ®Google Scholar
• Allen B, Singla A, Rizvi S, et al. Analysis of patient survival in a Phase I trial of systemic targeted α-therapy for metastatic melanoma. Immunotherapy. 2011;3(9):1041–1050.
   PubMed Web of Science ®Google Scholar
• Allen BJ, Raja C, Rizvi S, et al. Tumour anti-vascular alpha therapy: a mechanism for the regression of solid tumours in metastatic cancer. Phys Med Biol. 2007;52(13):L15–9.
   PubMed Web of Science ®Google Scholar
• Larsen RH, Murud KM, Akabani G, et al. 211At-and 131I-labeled bisphosphonates with high in vivo stability and bone accumulation. J Nucl Med. 1999;40:1197–1204.
   PubMed Web of Science ®Google Scholar
• Miederer M, McDevitt MR, Sgouros G, et al. Pharmacokinetics, dosimetry, and toxicity of the targetable atomic generator, 225Ac-HuM195, in nonhuman primates. J Nucl Med. 2004;45(1):129–137.
   PubMed Web of Science ®Google Scholar
• Jurcic JG, Rosenblat TL, McDevitt MR. Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac)-lintuzumab (anti-CD33; HuM195) in acute myeloid leukemia (AML). J Clin Oncol. 2011;29:Abstract 6516.
   Google Scholar
• Jurcic J, Ravandi F, Pagel JM, et al. Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac)-lintuzumab (anti-CD33) in combination with low-dose cytarabine (LDAC) for older patients with untreated acute myeloid leukemia (AML). Blood. 2013;122(21):1460–1460.
   Google Scholar
• Borchardt PE, Yuan RR, Miederer M, et al. Targeted actinium-225 in vivo generators for therapy of ovarian cancer. Cancer Res. 2003;63(16):5084–5090.
   PubMed Web of Science ®Google Scholar
• Heyerdahl H, Abbas N, Brevik EM, et al. Fractionated therapy of HER2-expressing breast and ovarian cancer xenografts in mice with targeted alpha emitting 227Th-DOTA-p-benzyl-trastuzumab. PLoS One. 2012;7:8.
   Web of Science ®Google Scholar
• Heyerdahl H, Abbas N, Sponheim K, et al. Targeted alpha therapy with ovarian cancer in nude mice 227Th-trastuzumab of intraperitoneal. Curr Radiopharm. 2013;6(2):106–116.
   PubMedGoogle Scholar
• Melhus KB, Larsen RH, Stokke T, et al. Evaluation of the binding of radiolabeled rituximab to CD20-positive lymphoma cells: an in vitro feasibility study concerning low-dose-rate radioimmunotherapy with the α -emitter 227 Th. Cancer Biother Radiopharm. 2007;22(4):469–479.
   PubMed Web of Science ®Google Scholar
• Dahle J, Jonasdottir TJ, Heyerdahl H, et al. Assessment of long-term radiotoxicity after treatment with the low-dose-rate alpha-particle-emitting radioimmunoconjugate 227Th- rituximab. Eur J Nucl Med Mol Imaging. 2010;37(1):93–102.
   PubMed Web of Science ®Google Scholar
• McDevitt M, Nikula T, Finn R. Bismuth labeled antibodies for therapy of leukemias, lymphomas, and carcinomas: preclinical studies. Tumor Target. 1996;2(Abstract):182.
   Google Scholar
• Schwartz J, Jaggi JS, O’Donoghue JA, et al. Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody. Phys Med Biol. 2011;56(3):721–733.
   PubMed Web of Science ®Google Scholar
• Jurcic JG, Larson SM, Sgouros G, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood. 2002;100(4):1233–1239.
   PubMed Web of Science ®Google Scholar
• Rosenblat TL, McDevitt MR, Mulford DA, et al. Sequential cytarabine and α-particle immunotherapy with bismuth-213–lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res. 2010;16(21):5303–5311.
   PubMed Web of Science ®Google Scholar
• Heeger S, Moldenhauer G, Egerer G, et al. Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: a preclinical model toward optimal consolidation therapy to eradicate minimal residual disease. Blood. 2010;116(20):4231–4239.
   PubMed Web of Science ®Google Scholar
• Roscher M, Hormann I, Leib O, et al. Targeted alpha-therapy using [Bi-213] anti-CD20 as novel treatment option for radio-and chemoresistant non-Hodgkin lymphoma cells. Oncotarget. 2013;4(2):218–230.
   PubMed Web of Science ®Google Scholar
• Heeger S, Moldenhauer G, Egerer G. Alpha-radioimmunotherapy of B-lineage non-Hodgkin’s lymphoma using 213Bi-labelled anti-CD19-and anti-CD20-CHX-A”-DTPA conjugates. Abstr Pap Am Chem Soc. 2003;225:U261.
   Web of Science ®Google Scholar
• Song EY, Abbas Rizvi SM, Qu CF, et al. Pharmacokinetics and toxicity of213Bi-labeled PAI2 in preclinical targeted alpha therapy for cancer. Cancer Biol Ther. 2007;6(6):898–904.
   PubMed Web of Science ®Google Scholar
• Allen BJ, Tian Z, Rizvi SMA, et al. Preclinical studies of targeted alpha therapy for breast cancer using 213Bi-labelled-plasminogen activator inhibitor type 2. Br J Cancer. 2003;88(6):944–950.
   PubMed Web of Science ®Google Scholar
• Qu CF, Song EY, Li Y, et al. Pre-clinical study of 213Bi labeled PAI2 for the control of micrometastatic pancreatic cancer. Clin Exp Metastasis. 2005;22(7):575–586.
   PubMed Web of Science ®Google Scholar
• Song EY, Qu CF, Rizvi SMA, et al. Bismuth-213 radioimmunotherapy with C595 anti-MUC1 monoclonal antibody in an ovarian cancer ascites model. Cancer Biol Ther. 2008;7(1):76–80.
   PubMed Web of Science ®Google Scholar
• Qu CF, Songl YJ, Rizvi SMA, et al. In vivo and in vitro inhibition of pancreatic cancer growth by targeted alpha therapy using 213Bi-CHX.A”-C595. Cancer Biol Ther. 2005;4(8):848–853.
   PubMed Web of Science ®Google Scholar
• Cordier D, Forrer F, Bruchertseifer F, et al. Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8, Met (O2) 11]-substance P: a pilot trial. Eur J Nucl Med Mol Imaging. 2010;37(7):1335–1344.
   PubMed Web of Science ®Google Scholar
• Morgenstern A, Krolicki L, Kunikowska J, et al. Targeted alpha therapy of glioblastoma multiforme: first clinical experience with 213Bi-substance P. J Nucl Med. 2014;55(supplement 1):390–390.
   Google Scholar
• Rizvi SMA, Allen BJ, Tian Z, et al. In vitro and preclinical studies of targeted alpha therapy (TAT) for colorectal cancer. Color Dis. 2001;3(5):345–353.
   PubMedGoogle Scholar
• Li Y, Wang J, Abbas Rizvi SM, et al. In vitro targeting of NG2 antigen by 213Bi-9.2.27 α-immunoconjugate induces cytotoxicity in human uveal melanoma cells. Investig Ophthalmol Vis Sci. 2005;46(12):4365–4371.
   PubMed Web of Science ®Google Scholar
• Raja C, Graham P, Abbas Rizvi S, et al. Interim analysis of toxicity and response in phase 1 trial of systemic targeted alpha therapy for metastatic melanoma. Cancer Biol Ther. 2007;6(6):846–852.
   PubMed Web of Science ®Google Scholar
• Allen BJ, Raja C, Rizvi S, et al. Intralesional targeted alpha therapy for metastatic melanoma. Cancer Biol Ther. 2005;4(12):1318–1324.
   PubMed Web of Science ®Google Scholar
• Fichou N. Single-dose anti-CD138 radioimmunotherapy: bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model. Front Med. 2015;2(76):1–11.
   Google Scholar
• Li Y, Tian Z, Rizvi SMA, et al. In vitro and preclinical targeted alpha therapy of human prostate cancer with Bi-213 labeled J591 antibody against the prostate specific membrane antigen. Prostate Cancer Prostatic Dis. 2002;5(1):36–46.
   PubMed Web of Science ®Google Scholar
• Adams GP, Shaller CC, Chappell LL, et al. Delivery of the α-emitting radioisotope bismuth-213 to solid tumors via single-chain Fv and diabody molecules. Nucl Med Biol. 2000;27(4):339–346.
   PubMed Web of Science ®Google Scholar
• Tan Z, Chen P, Schneider N, et al. Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb-trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice. Int J Oncol. 2012;40(6):1881–1888.
   PubMed Web of Science ®Google Scholar
• Yong K, Brechbiel M. Application of 212Pb for Targeted α-particle Therapy (TAT): pre-clinical and mechanistic understanding through to clinical translation. AIMS Med Sci. 2015;2(3):228–245.
   PubMedGoogle Scholar
• Meredith R, Torgue J, Shen S, et al. Dose escalation and dosimetry of first-in-human α radioimmunotherapy with 212Pb-TCMC-trastuzumab. J Nucl Med. 2014;55(10):1636–1642.
   PubMed Web of Science ®Google Scholar
• Meredith RF, Torgue J, Azure MT, et al. Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm. 2013;29(1):12–18.
   PubMed Web of Science ®Google Scholar
• Zalutsky MR, Garg PK, Friedman HS, et al. Labeling monoclonal antibodies and F (ab ’) 2 fragments with the a-particle-emitting nuclide astatine-211: Preservation of immunoreactivity and in vivo localizing capacity. Proc Natl Acad Sci. 1989;86(18): 7149–7153.
   PubMed Web of Science ®Google Scholar
• Zalutsky MR, Stabin MG, Larsen RH, et al. Tissue distribution and radiation dosimetry of astatine-211-labeled chimeric 81C6, an α-particle-emitting immunoconjugate. Nucl Med Biol. 1997;24(3):255–261.
   PubMed Web of Science ®Google Scholar
• Zalutsky MR, Reardon DA, Akabani G, et al. Clinical experience with α-particle–emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J Nucl Med. 2007;49(1):30–38.
   PubMed Web of Science ®Google Scholar
• Elgqvist J, Andersson H, Bäck T, et al. Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211 At-MX35 F (ab′) 2: therapeutic efficacy and myelotoxicity. Nucl Med Biol. 2006;33(8):1065–1072.
   PubMed Web of Science ®Google Scholar
• Andersson H, Cederkrantz E, Bäck T, et al. Intraperitoneal α-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of 211At-MX35 F (ab′) 2—a phase I study. J Nucl Med. 2009;50(7):1153–1160.
   PubMed Web of Science ®Google Scholar
• Andersson H, Lindegren S, Bäck T, et al. The curative and palliative potential of the monoclonal antibody MOv18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts-a long-term study. Acta Oncol (Madr). 2000;39(6):741–745.
   Web of Science ®Google Scholar
• Reist CJ, Foulon CF, Alston K, et al. Astatine-211 labeling of internalizing anti-EGFRvIII monoclonal antibody using N-succinimidyl 5-[211 At] astato-3-pyridinecarboxylate. Nucl Med Biol. 1999;26(4):405–411.
   PubMed Web of Science ®Google Scholar
• Robinson MK, Shaller C, Garmestani K, et al. Effective treatment of established human breast tumor xenografts in immunodeficient mice with a single dose of the α-emitting radioisotope astatine-211 conjugated to anti-HER2/neu diabodies. Clin Cancer Res. 2008;14(3):875–882.
   PubMed Web of Science ®Google Scholar
• Steffen A-C, Almqvist Y, Chyan M-K, et al. Biodistribution of 211At labeled HER-2 binding affibody molecules in mice. Oncol Rep. 2007;17(5):1141–1147.
   PubMed Web of Science ®Google Scholar
• Henriksen G, Breistol K, Bruland OS, et al. Significant antitumor effect from bone-seeking, alpha-particle-emitting (223)Ra demonstrated in an experimental skeletal metastases model. Cancer Res. 2002;62(11):3120–3125.
   PubMed Web of Science ®Google Scholar
• Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–223.
   PubMed Web of Science ®Google Scholar
• Nilsson S, Larsen RH, Fosså SD, et al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11(12):4451–4459.
   PubMed Web of Science ®Google Scholar
• Pozzi OR, Zalutsky MR. Radiopharmaceutical chemistry of targeted radiotherapeutics, part 2 : radiolytic effects of 211At alpha-particles influence N-succinimidyl 3-211At-astatobenzoate synthesis. J Nucl Med. 2005;46(8):1393–1400.
   PubMed Web of Science ®Google Scholar
• Pozzi OR, Zalutsky MR. Radiopharmaceutical chemistry of targeted radiotherapeutics, Part 3: alpha-particle-induced radiolytic effects on the chemical behavior of 211At. J Nucl Med. 2007;48(7):1190–1196.
   PubMed Web of Science ®Google Scholar
• Boyd M, Sorensen A, McCluskey AG, et al. Radiation quality-dependent bystander effects elicited by targeted radionuclides. J Pharm Pharmacol. 2008;60(8):951–958.
   PubMed Web of Science ®Google Scholar
• Mancuso M, Pasquali E, Leonardi S, et al. Oncogenic bystander radiation effects in patched heterozygous mouse cerebellum. Proc Natl Acad Sci. 2008;105(34):12445–12450.
   PubMed Web of Science ®Google Scholar
• Havaki S, Kotsinas A, Chronopoulos E, et al. The role of oxidative DNA damage in radiation induced bystander effect. Cancer Lett. 2015;356(1):43–51. Elsevier Ireland Ltd.
   PubMed Web of Science ®Google Scholar
• De Kruijff R, Wolterbeek H, Denkova A. A critical review of alpha radionuclide therapy—how to deal with recoiling daughters? Pharmaceuticals. 2015;8(2):321–336.
   Google Scholar
• Lewis B, Chalhoub E, Chalouhy C, et al. Radium-223 in bone-metastatic prostate cancer: current data and future prospects. Oncology (Williston Park). 2015;29(7):483–488.
   PubMed Web of Science ®Google Scholar
• Miederer M, Scheinberg DA, McDevitt MR. Realizing the potential of the actinium-225 radionuclide generator in targeted alpha particle therapy applications. Adv Drug Deliv Rev. 2008;60(12):1371–1382.
   PubMed Web of Science ®Google Scholar
• McDevitt MR, Ma D, Lai LT, et al. Tumor therapy with targeted atomic nanogenerators. Science. 2001;294:1537–1541.
   PubMed Web of Science ®Google Scholar
• Sgouros G, Roeske JC, Mcdevitt MR, et al. MIRD pamphlet no. 22 - radiobiology and dosimetry of alpha- particle emitters for targeted radionuclide therapy. J Nucl Med. 2010;51(22):311–328.
   PubMed Web of Science ®Google Scholar
• Huang C-Y, Oborn BM, Guatelli S, et al. Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy. Med Phys. 2012;39(3):1282–1288.
   PubMed Web of Science ®Google Scholar
• Huang CY, Guatelli S, Oborn BM, et al. Microdosimetry for targeted alpha therapy of cancer. Comput Math Methods Med. 2012;2012.
   Google Scholar
• Bäck T, Jacobsson L. The alpha-camera: a quantitative digital autoradiography technique using a charge-coupled device for ex vivo high-resolution bioimaging of alpha-particles. J Nucl Med. 2010;51(10):1616–1623.
   PubMed Web of Science ®Google Scholar
• FDA Approves Xofigo for Advanced Prostate Cancer [Internet]. 2013. Available from: http://www.fda.gov/NewsEvents.
   Google Scholar
• Bruland ÒS, Nilsson S, Fisher DR, et al. High-linear energy transfer irradiation targeted to skeletal metastases by alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res. 2006;12(21):6250–6257.
   Web of Science ®Google Scholar
• Wadas TJ, Pandya DN, Solingapuram Sai KK, et al. Molecular targeted α-particle therapy for oncologic applications. Am J Roentgenol. 2014;203:253–260.
   PubMed Web of Science ®Google Scholar
• McDevitt MR, Sgouros G, Finn RD, et al. Radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med. 1998;25(9):1341–1351.
   PubMedGoogle Scholar
• Apostolidis C, Molinet R, McGinley J, et al. Cyclotron production of Ac-225 for targeted alpha therapy. Appl Radiat Isot. 2005;62(3):383–387.
   PubMed Web of Science ®Google Scholar
• McDevitt MR, Ma D, Simon J, et al. Design and synthesis of 225Ac radioimmunopharmaceuticals. Appl Radiat Isot. 2002;57:841–847.
   PubMed Web of Science ®Google Scholar
• Maguire WF, McDevitt MR, Smith-Jones PM, et al. Efficient 1-step radiolabeling of monoclonal antibodies to high specific activity with 225Ac for α-particle radioimmunotherapy of cancer. J Nucl Med. 2014;55(9):1492–1498.
   PubMed Web of Science ®Google Scholar
• Pippin CG, Gansow OA, Brechbiel MW, et al. Recovery of Bi-213 from an Ac-225 cow: application to the radiolabeling of antibodies with Bi-213. Chemists’ Views of Imaging Centers. Springer US. 1995;315–322.
   Google Scholar
• McDevitt MR, Finn RD, Ma D, et al. Preparation of (alpha)-emitting (213) Bi-labeled antibody constructs for clinical use. J Nucl Med. 1999;40(10):1722.
   PubMed Web of Science ®Google Scholar
• Guérard F, Gestin J-F, Brechbiel MW. Production of (211At)-astatinated radiopharmaceuticals and applications in targeted α-particle therapy. Cancer Biother Radiopharm. 2013;28(1):1–20.
   PubMed Web of Science ®Google Scholar
• Zalutsky MR, Pruszynski M. Astatine-211: production and availability. Curr Radiopharm. 2011;4(3):177–185.
   PubMedGoogle Scholar
• Zalutsky MR, Vaidyanathan G. Astatine-211-labeled radiotherapeutics an emerging approach to targeted alpha-particle radiotherapy. Curr Pharm Des. 2000;6(14):1433–1455.
   PubMed Web of Science ®Google Scholar
• Zalutsky MR, Zhao X, Alston KL, et al. High-level production of α-particle–emitting 211At and preparation of 211At-labeled antibodies for clinical use. J Nucl Med. 2001;42(10):1508–1516.
   PubMed Web of Science ®Google Scholar
• Vaidyanathan G, Larsen RH, Zalutsky MR. 5-[211At] Astato-2′-deoxyuridine, an α-particle-emitting endoradiotherapeutic agent undergoing DNA incorporation. Cancer Res. 1996;56(6):1204–1209.
   PubMed Web of Science ®Google Scholar
• Foulon CF, Alston KL, Zalutsky MR. Astatine-211-labeled biotin conjugates resistant to biotinidase for use in pretargeted radioimmunotherapy. Nucl Med Biol. 1998;25(2):81–88.
   PubMed Web of Science ®Google Scholar
• Bloomer WD, McLaughlin WH, Neirinckx RD, et al. Astatine-211–tellurium radiocolloid cures experimental malignant ascites. Science. 1981;212(4492):340–341.
   PubMed Web of Science ®Google Scholar
• Link EM, Carpenter RN. 211At-methylene blue for targeted radiotherapy of human melanoma xenografts: treatment of micrometastases. Cancer Res. 1990;50(10):2963–2968.
   PubMed Web of Science ®Google Scholar
• Vaidyanathan G, Zalutsky MR. No-carrier-added meta-[123 I] iodobenzylguanidine: synthesis and preliminary evaluation. Nucl Med Biol. 1995;22(1):61–64.
   PubMed Web of Science ®Google Scholar
• Murud KM, Larsen RH, Bruland OS, et al. Influence of pretreatment with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APB) on organ uptake of 211 At and 125 I-labeled amidobisphosphonates in mice. Nucl Med Biol. 1999;26(7):791–794.
   PubMed Web of Science ®Google Scholar
• Larson SM, Carrasquillo JA, Cheung N-KV, et al. Radioimmunotherapy of human tumours. Nat Rev Cancer. 2015;15(6):347–360. Nature Publishing Group.
   PubMed Web of Science ®Google Scholar
• Holliger P, Hudson PJ. Engineered antibody fragments and the rise of single domains. Nat Biotechnol. 2005;23(9):1126–1136.
   PubMed Web of Science ®Google Scholar
• Müller C, Schibli R. Prospects in folate receptor-targeted radionuclide therapy. Front Oncol. 2013;3:249.
   PubMedGoogle Scholar
• Vergote I, Leamon CP. Vintafolide: a novel targeted therapy for the treatment of folate receptor expressing tumors. Ther Adv Med Oncol. 2015;7(4):206–218.
   PubMed Web of Science ®Google Scholar
• Dong C, Liu Z, Wang F. Peptide-based radiopharmaceuticals for targeted tumor therapy. Curr Med Chem. 2014;21(1):139–152.
   PubMed Web of Science ®Google Scholar
• Löfblom J, Feldwisch J, Tolmachev V, et al. Affibody molecules: engineered proteins for therapeutic, diagnostic and biotechnological applications. FEBS Lett. 2010;584(12):2670–2680. Federation of European Biochemical Societies.
   PubMed Web of Science ®Google Scholar
• Hamers-Casterman C, Atarhouch T, Muyldermans S, et al. Naturally occurring antibodies devoid of light chains. Nature. 1993;363(6428):446–448.
   PubMed Web of Science ®Google Scholar
• De Vos J, Devoogdt N, Lahoutte T, et al. Camelid single-domain antibody-fragment engineering for (pre)clinical in vivo molecular imaging applications: adjusting the bullet to its target. Expert Opin Biol Ther. 2013;13(8):1149–1160.
   PubMed Web of Science ®Google Scholar
• D’Huyvetter M, Xavier C, Caveliers V, et al. Radiolabeled nanobodies as theranostic tools in targeted radionuclide therapy of cancer. Expert Opin Drug Deliv. 2014;131(12):1–16. Informa UK, Ltd.
   Google Scholar
• Huang L, Gainkam LOT, Caveliers V, et al. SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression. Mol Imaging Biol. 2008;10(3):167–175.
   PubMed Web of Science ®Google Scholar
• Vaneycken I, Govaert J, Vincke C, et al. In vitro analysis and in vivo tumor targeting of a humanized, grafted nanobody in mice using pinhole SPECT/micro-CT. J Nucl Med. 2010;51(7):1099–1106.
   PubMed Web of Science ®Google Scholar
• Vaneycken I, Devoogdt N, Van Gassen N, et al. Preclinical screening of anti-HER2 nanobodies for molecular imaging of breast cancer. Faseb J. 2011;25(7):2433–2446.
   PubMed Web of Science ®Google Scholar
• Tchouate Gainkam LO, Caveliers V, Devoogdt N, et al. Localization, mechanism and reduction of renal retention of technetium-99m labeled epidermal growth factor receptor-specific nanobody in mice. Contrast Media Mol Imaging. 2011;6(2):85–92.
   PubMed Web of Science ®Google Scholar
• Schoonooghe S, Laoui D, Van Ginderachter JA, et al. Novel applications of nanobodies for in vivo bio-imaging of inflamed tissues in inflammatory diseases and cancer. Immunobiology. 2012;217(12):1266–1272. Elsevier GmbH.
   PubMed Web of Science ®Google Scholar
• D’Huyvetter M, Vincke C, Xavier C, et al. Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody. Theranostics. 2014;4(7):708–720.
   PubMed Web of Science ®Google Scholar
• Keyaerts M, Xavier C, Heemskerk J, et al. Phase I study of 68Ga-HER2-nanobody for PET/CT assessment of HER2 expression in breast carcinoma. J Nucl Med. 2015;57(1):27–33.
   PubMed Web of Science ®Google Scholar
• Lemaire M, D’Huyvetter M, Lahoutte T, et al. Imaging and radioimmunotherapy of multiple myeloma with anti-idiotypic nanobodies. Leukemia. 2014;28(2):444–447.
   PubMed Web of Science ®Google Scholar
• Pruszynski M, Koumarianou E, Vaidyanathan G, et al. Improved tumor targeting of anti-HER2 nanobody through N-succinimidyl 4-guanidinomethyl-3-iodobenzoate radiolabeling. J Nucl Med. 2014;55(4):650–656.
   PubMed Web of Science ®Google Scholar
• Choi J, Vaidyanathan G, Koumarianou E, et al. N-succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization. Nucl Med Biol. 2014;41(10):802–812.
   PubMed Web of Science ®Google Scholar
• Choi J, Vaidyanathan G, Koumarianou E, et al. A 211At-labeled nanobody for α-particle therapy of HER2-expressing cancers. J Nucl Med. 2015;56(Supplement 3):171.
   PubMed Web of Science ®Google Scholar
• Zheng F, Put S, Bouwens L, et al. Molecular imaging with macrophage CRIg-targeting nanobodies for early and preclinical diagnosis in a mouse model of rheumatoid arthritis. J Nucl Med. 2014;55(5):824–829.
   PubMed Web of Science ®Google Scholar
• Aneheim E, Albertsson P, Bäck T, et al. Automated astatination of biomolecules – a stepping stone towards multicenter clinical trials. Sci Rep. 2015;5:12025. Nature Publishing Group
   PubMed Web of Science ®Google Scholar
• Oliveira S, Schiffelers RM, Van Der Veeken J, et al. Downregulation of EGFR by a novel multivalent nanobody-liposome platform. J Control Release. 2010;145(2):165–175. Elsevier B.V.
   PubMed Web of Science ®Google Scholar