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Published Online:https://doi.org/10.4155/fmc.11.14

Positron emission tomography, with its high sensitivity and resolution, is growing rapidly as an imaging technology for the diagnosis of many disease states. The success of this modality is reliant on instrumentation and the development of effective and novel targeted probes. Initially, research in this area was focused on what we will define in this article as ‘standard’ PET isotopes (carbon-11, nitrogen-13, oxygen-15 and fluorine-18), but the short half-lives of these isotopes limit radiopharmaceutical development to those that probe rapid biological processes. To overcome these limitations, there has been a rise in nonstandard isotope probe development in recent years. This review focuses on the biological probes and processes that have been examined, in additiom to the preclinical and clinical findings with nonstandard radiometals: copper-64, zirconium-89, and yttrium-86.

Papers of special note have been highlighted as: ▪ of interest

Bibliography

  • Holland JP, Williamson MJ, Lewis JS. Unconventional nuclides for radiopharmaceuticals. Mol. Imaging9(1),1–20 (2010).
  • Meijs WE, Herscheid JDM, Haisma HJ, Wijbrandts F, van Langevelde F, van Leuffen PJ. Production of highly pure no-carrier added 89Zr for the labeling of antibodies and a positron emitter. Appl. Radiat. Isot.45,1143–1147 (1994).▪ Provides details of zirconium-89 production.
  • Dejesus OT, Nickles RJ. Production and purification of Zr-89, a potential pet antibody label. Appl. Radiat. Isot.41(8),789–790 (1990).
  • Avila-Rodriguez MA, Nye JA, Nickles RJ. Production and separation of noncarrier-added 86Y from enriched 86Sr targets. Appl. Radiat. Isot.66(1),9–13 (2008).
  • Reischl G, Rosch F, Machulla HJ. Electrochemical separation and purification of yttrium-86. Radiochimica Acta90(4),225–228 (2002).
  • Sun X, Anderson CJ. Production and applications of copper-64 radiopharmaceuticals. Methods Enzymol.386,237–261 (2004).
  • McCarthy DW, Shefer RE, Klinkowstein RE et al. Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol.24(1),35–43 (1997).▪ Provides details of copper-64 production.
  • Wadas TJ, Wong EH, Weisman GR, Anderson CJ. Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease. Chem. Rev.110(5),2858–2902 (2010).▪ Provides details on chelators for radiometals.
  • Pal S, Chattopadhyay S, Das MK, Sudersanan M. Production and separation of no-carrier-added radioactive tracers of yttrium, strontium and rubidium from heavy-ion irradiated germanium target: applicability to the standardization of a separation technique for production of positron-emitting radionuclide Y-86. Appl. Radiat. Isot.64(12),1521–1527 (2006).
  • 10  Yoo J, Tang L, Perkins TA et al. Preparation of high specific activity Y-86 using a small biomedical cyclotron. Nucl. Med. Biol.32(8),891–897 (2005).
  • 11  Zweit J, Downey S, Sharma HL. Production of no-carrier-added zirconium-89 for positron emission tomography. Appl. Radiat. Isot.42(2),199–201 (1991).
  • 12  Hohn A, Zimmermann K, Schaub E, Hirzel W, Schubiger PA, Schibli R. Production and separation of ‘‘nonstandard’’ PET nuclides at a large cyclotron facility: the experiences at the Paul Scherrer Institute in Switzerland. Q. J. Nucl. Med. Mol. Imaging52(2),145–150 (2008).
  • 13  Link JM, Krohn KA, Eary JF. 89Zr for antibody labeling and positron tomography. J. Labeled Compd Radiopharm.23,1296–1297 (1986).
  • 14  Verel I, Visser GW, Boellaard R, Stigter-van Walsum M, Snow GB, van Dongen GA. 89Zr immuno-PET: comprehensive procedures for the production of 89Zr-labeled monoclonal antibodies. J. Nucl. Med.44(8),1271–1281 (2003).▪ Overview of zirconium-89 antibody labeling.
  • 15  Wadas TJ, Wong EH, Weisman GR, Anderson CJ. Copper chelation chemistry and its role in copper radiopharmaceuticals. Curr. Pharm. Des.13(1),3–16 (2007).
  • 16  Zinn KR, Chaudhuri TR, Cheng TP, Morris JS, Meyer WA, Jr. Production of no-carrier-added 64Cu from zinc metal irradiated under boron shielding. Cancer73(Suppl. 3),774–778 (1994).
  • 17  Szelecsenyi F, Blessing G, Qaim SM. Excitation function of proton induced nuclear reactions on enriched 61Ni and 64Ni: possibility of production of no-carrier-added 61Cu and 64Cu at a small cyclotron. Appl. Radiat. Isot.44,575–580 (1993).
  • 18  Smith SV, Waters D, DiBartolo N. Carrier-free copper-64 isolated from Ga-67 waste for use in PET and therapy. J. Nucl. Med.37(5),894–894 (1996).
  • 19  Qaim SM, Bisinger T, Hilgers K, Nayak D, Coenen HH. Positron emission intensities in decay of 64Cu, 76Br, and 124I. Radiochimica Acta95,67–73 (2007).
  • 20  Firestone RB, Baglin CM, Chu SYF. In: Table of Isotopes, Volumes 1–2. Shirley VS (Ed.). John Wiley & Sons, Inc., NY, USA (1996).
  • 21  Holland JP, Sheh Y, Lewis JS. Standardized methods for the production of high specific-activity zirconium-89. Nucl. Med. Biol.36(7),729–739 (2009).
  • 22  Kandil SA, Scholten B, Saleh AM, Youssef SM, Qaim SM, Coenen HH. A comparative study on the separation of radiozirconium via ion-exchange and solvent extraction techniques, with particular reference to the production of 88Zr and 89Zr in proton induced reactions on yttrium. J. Radioanal. Nucl. Chem.274,45–52 (2007).
  • 23  Nayak TK, Brechbiel MW. Radioimmunoimaging with longer-lived positron-emitting radionuclides: potentials and challenges. Bioconjug. Chem.20(5),825–841 (2009).▪ Summary of immuno-PET.
  • 24  Perk LR, Visser OJ, Stigter-van Walsum M et al. Preparation and evaluation of (89)Zr-Zevalin for monitoring of (90)Y-Zevalin biodistribution with positron emission tomography. Eur. J. Nucl. Med. Mol. Imaging33(11),1337–1345 (2006).
  • 25  Welch MJ, Laforest R, Lewis JS. Production of nonstandard PET radionuclides and the application of radiopharmaceuticals labeled with these nuclides. Ernst Schering Res. Found. Workshop (62), 159–181 (2007).
  • 26  Moi MK, Meares CF, McCall MJ, Cole WC, DeNardo SJ. Copper chelates as probes of biological systems: stable copper complexes with a macrocyclic bifunctional chelating agent. Anal. Biochem.148(1),249–253 (1985).
  • 27  Shokeen M, Anderson CJ. Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET). Acc. Chem. Res.42(7),832–841 (2009).
  • 28  Hoffman TJ, Smith CJ. True radiotracers: Cu-64 targeting vectors based upon bombesin peptide. Nucl. Med. Biol.36(6),579–585 (2009).
  • 29  Anderson CJ, Ferdani R. Copper-64 radiopharmaceuticals for PET imaging of cancer: advances in preclinical and clinical research. Cancer Biother. Radiopharm.24(4),379–393 (2009).
  • 30  Tatum JL, Kelloff GJ, Gillies RJ et al. Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int. J. Radiat. Biol.82(10),699–757 (2006).
  • 31  Lewis JS, Laforest R, Dehdashti F, Grigsby PW, Welch MJ, Siegel BA. An imaging comparison of 64Cu-ATSM and 60Cu-ATSM in cancer of the uterine cervix. J. Nucl. Med.49(7),1177–1182 (2008).
  • 32  Dehdashti F, Mintun MA, Lewis JS et al.In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Eur. J. Nucl. Med. Mol. Imaging30(6),844–850 (2003).
  • 33  Dehdashti F, Grigsby PW, Mintun MA, Lewis JS, Siegel BA, Welch MJ. Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response – a preliminary report. Int. J. Radiat. Oncol. Biol. Phys.55(5),1233–1238 (2003).
  • 34  Lewis JS, Connett JM, Garbow JR et al. Copper-64-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) for the prevention of tumor growth at wound sites following laparoscopic surgery: monitoring therapy response with microPET and magnetic resonance imaging. Cancer Res.62(2),445–449 (2002).
  • 35  Krohn KA, Link JM, Mason RP. Molecular imaging of hypoxia. J. Nucl. Med.49(Suppl. 2),129S–148S (2008).
  • 36  Vavere AL, Lewis JS. Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans. (43), 4893–4902 (2007).
  • 37  Lapi SE, Voller TF, Welch MJ. Positron emission tomography imaging of hypoxia. PET Clin.4(1),39–47 (2009).
  • 38  Lewis J, Laforest R, Buettner T et al. Copper-64-diacetyl-bis(N4-methylthiosemicarbazone): an agent for radiotherapy. Proc. Natl Acad. Sci. USA98(3),1206–1211 (2001).
  • 39  Fodero-Tavoletti MT, Villemagne VL, Paterson BM et al. Bis(thiosemicarbazonato) Cu-64 complexes for positron emission tomography imaging of Alzheimer’s disease. J. Alzheimers Dis.20(1),49–55 (2010).
  • 40  Lim S, Paterson BM, Fodero-Tavoletti MT et al. A copper radiopharmaceutical for diagnostic imaging of Alzheimer’s disease: a bis(thiosemicarbazonato)copper(II) complex that binds to amyloid-β plaques. Chem. Commun. (Camb.)46(30),5437–5439 (2010).
  • 41  Reubi JC. Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging. J. Nucl. Med.36(10),1825–1835 (1995).
  • 42  Lamberts SW, Krenning EP, Reubi JC. The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr. Rev.12(4),450–482 (1991).
  • 43  Anderson CJ, Pajeau TS, Edwards WB, Sherman EL, Rogers BE, Welch MJ. In vitro and in vivo evaluation of copper-64-octreotide conjugates.J. Nucl. Med.36(12),2315–2325 (1995).
  • 44  Dehdashti F, Anderson CJ, Trask DD et al. Initial results with PET imaging using Cu-64-labeled TETA-octreotide in patients with carinoid tumor. J. Nucl. Med.38,103P (1997).
  • 45  Lewis JS, Lewis MR, Srinivasan A, Schmidt MA, Wang J, Anderson CJ. Comparison of four 64Cu-labeled somatostatin analogs in vitro and in a tumor-bearing rat model: evaluation of new derivatives for positron emission tomography imaging and targeted radiotherapy. J. Med. Chem.42(8),1341–1347 (1999).
  • 46  Clifford T, Boswell CA, Biddlecombe GB, Lewis JS, Brechbiel MW. Validation of a novel CHX-A’’ derivative suitable for peptide conjugation: small animal PET/CT imaging using yttrium-86-CHX-A’’-octreotide. J. Med. Chem.49(14),4297–4304 (2006).
  • 47  Gugger M, Reubi JC. Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast. Am. J. Pathol.155(6),2067–2076 (1999).
  • 48  Markwalder R, Reubi JC. Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res.59(5),1152–1159 (1999).
  • 49  Scheffel U, Pomper MG. PET imaging of GRP receptor expression in prostate cancer. J. Nucl. Med.45(8),1277–1278 (2004).
  • 50  Reubi JC, Wenger S, Schmuckli-Maurer J, Schaer JC, Gugger M. Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), β-ALA(11), PHE(13), NLE(14)] bombesin(6–14). Clin. Cancer Res.8(4),1139–1146 (2002).
  • 51  Parry JJ, Andrews R, Rogers BE. MicroPET imaging of breast cancer using radiolabeled bombesin analogs targeting the gastrin-releasing peptide receptor. Breast Cancer Res. Treat.101(2),175–183 (2007).
  • 52  Rogers BE, Bigott HM, McCarthy DW et al. MicroPET imaging of a gastrin-releasing peptide receptor-positive tumor in a mouse model of human prostate cancer using a 64Cu-labeled bombesin analog. Bioconjug. Chem.14(4),756–763 (2003).
  • 53  Parry JJ, Kelly TS, Andrews R, Rogers BE. In vitro and in vivo evaluation of 64Cu-labeled DOTA-linker-bombesin(7–14) analogs containing different amino acid linker moieties. Bioconjug. Chem.18(4),1110–1117 (2007).
  • 54  Yang YS, Zhang X, Xiong Z, Chen X. Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma. Nucl. Med. Biol.33(3),371–380 (2006).
  • 55  Chen X, Park R, Hou Y et al. MicroPET and autoradiographic imaging of GRP receptor expression with 64Cu-DOTA-[Lys3]bombesin in human prostate adenocarcinoma xenografts. J. Nucl. Med.45(8),1390–1397 (2004).
  • 56  Prasanphanich AF, Nanda PK, Rold TL et al. [64Cu-NOTA-8-Aoc-BBN(7–14)NH2] targeting vector for positron-emission tomography imaging of gastrin-releasing peptide receptor-expressing tissues. Proc. Natl Acad. Sci. USA104(30),12462–12467 (2007).
  • 57  Garrison JC, Rold TL, Sieckman GL et al. In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. J. Nucl. Med.48(8),1327–1337 (2007).
  • 58  Hwang R, Varner J. The role of integrins in tumor angiogenesis. Hematol. Oncol. Clin. North Am.18(5),991–1006 (2004).
  • 59  Tucker GC. αv integrin inhibitors and cancer therapy. Curr. Opin. Investig. Drugs4(6),722–731 (2003).
  • 60  Sprague JE, Kitaura H, Zou W et al. Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide. J. Nucl. Med.48(2),311–318 (2007).
  • 61  Varner JA, Cheresh DA. Tumor angiogenesis and the role of vascular cell integrin αvβ3. Important Adv. Oncol.69–87 (1996).
  • 62  Ruoslahti E. RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol.12,697–715 (1996).
  • 63  Wei L, Ye Y, Wadas TJ et al. (64)Cu-labeled CB-TE2A and diamsar-conjugated RGD peptide analogs for targeting angiogenesis: comparison of their biological activity. Nucl. Med. Biol.36(3),277–285 (2009).
  • 64  Chen X, Liu S, Hou Y et al. MicroPET imaging of breast cancer αv-integrin expression with 64Cu-labeled dimeric RGD peptides. Mol. Imaging Biol.6(5),350–359 (2004).
  • 65  Wu Y, Zhang X, Xiong Z et al. MicroPET imaging of glioma integrin {α}v{β}3 expression using (64)Cu-labeled tetrameric RGD peptide. J. Nucl. Med.46(10),1707–1718 (2005).
  • 66  Wadas TJ, Deng H, Sprague JE, Zheleznyak A, Weilbaecher KN, Anderson CJ. Targeting the αvβ3 integrin for small-animal PET/CT of osteolytic bone metastases. J. Nucl. Med.50(11),1873–1880 (2009).
  • 67  Gao L, Deng H, Zhao H et al. HTLV-1 tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition. Blood106(13),4294–4302 (2005).
  • 68  Siegrist W, Solca F, Stutz S et al. Characterization of receptors for α-melanocyte-stimulating hormone on human melanoma cells. Cancer Res.49(22),6352–6358 (1989).
  • 69  Tatro JB, Wen Z, Entwistle ML et al. Interaction of an α-melanocyte-stimulating hormone-diphtheria toxin fusion protein with melanotropin receptors in human melanoma metastases. Cancer Res.52(9),2545–2548 (1992).
  • 70  Jiang J, Sharma SD, Fink JL, Hadley ME, Hruby VJ. Melanotropic peptide receptors: membrane markers of human melanoma cells. Exp. Dermatol.5(6),325–333 (1996).
  • 71  Tatro JB, Atkins M, Mier JW et al. Melanotropin receptors demonstrated in situ in human melanoma. J. Clin. Invest.85(6),1825–1832 (1990).
  • 72  Wei L, Zhang X, Gallazzi F et al. Melanoma imaging using (111)In-, (86)Y- and (68)Ga-labeled CHX-A’’-Re(Arg-11)CCMSH. Nucl. Med. Biol.36(4),345–354 (2009).
  • 73  Ghanem GE, Comunale G, Libert A, Vercammen-Grandjean A, Lejeune FJ. Evidence for α-melanocyte-stimulating hormone (α-MSH) receptors on human malignant melanoma cells. Int. J. Cancer41(2),248–255 (1988).
  • 74  Cornish J, Callon KE, Mountjoy KG et al. α-melanocyte-stimulating hormone is a novel regulator of bone. Am. J. Physiol. Endocrinol. Metab.284(6),E1181–E1190 (2003).
  • 75  Sawyer TK, Castrucci AM, Staples DJ et al. Structure–activity relationships of [Nle4, D-Phe7]α-MSH. Discovery of a tripeptidyl agonist exhibiting sustained bioactivity. Ann. NY Acad. Sci.680,597–599 (1993).
  • 76  McQuade P, Miao Y, Yoo J, Quinn TP, Welch MJ, Lewis JS. Imaging of melanoma using 64Cu- and 86Y-DOTA-ReCCMSH(Arg11), a cyclized peptide analog of α-MSH. J. Med. Chem.48(8),2985–2992 (2005).
  • 77  Wei L, Butcher C, Miao Y et al. Synthesis and biologic evaluation of 64Cu-labeled rhenium-cyclized α-MSH peptide analog using a cross-bridged cyclam chelator. J. Nucl. Med.48(1),64–72 (2007).
  • 78  Nilsson FY, Tolmachev V. Affibody molecules: new protein domains for molecular imaging and targeted tumor therapy. Curr. Opin. Drug Discov. Devel.10(2),167–175 (2007).
  • 79  Cheng Z, De Jesus OP, Kramer DJ et al.64Cu-labeled affibody molecules for imaging of HER2 expressing tumors. Mol. Imaging Biol.12(3),316–324 (2009).
  • 80  Miao Z, Ren G, Liu H, Jiang L, Cheng Z. Small-animal PET imaging of human epidermal growth factor receptor-positive tumor with a 64Cu labeled affibody protein. Bioconjug. Chem.21(5),947–954 (2010).
  • 81  Forster GJ, Engelbach MJ, Brockmann JJ et al. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor-positive tumours: comparison of (86)Y-DOTATOC and (111)In-DTPA-octreotide. Eur. J. Nucl. Med.28(12),1743–1750 (2001).
  • 82  Jamar F, Barone R, Mathieu I et al. 86Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487) – a Phase I clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur. J. Nucl. Med. Mol. Imaging30(4),510–518 (2003).
  • 83  Reichert JM. Monoclonal antibodies as innovative therapeutics. Curr. Pharm. Biotechnol.9(6),423–430 (2008).
  • 84  van Dongen GA, Vosjan MJ. Immuno-positron emission tomography: shedding light on clinical antibody therapy. Cancer Biother. Radiopharm.25(4),375–385 (2010).
  • 85  Wu AM, Olafsen T. Antibodies for molecular imaging of cancer. Cancer J.14(3),191–197 (2008).
  • 86  Williams LE, Wu AM, Yazaki PJ et al. Numerical selection of optimal tumor imaging agents with application to engineered antibodies. Cancer Biother. Radiopharm.16(1),25–35 (2001).
  • 87  McCabe KE, Wu AM. Positive progress in immunoPET – not just a coincidence. Cancer Biother. Radiopharm.25(3),253–261 (2010).
  • 88  Brekke OH, Sandlie I. Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat. Rev. Drug Discov.2(1),52–62 (2003).
  • 89  Reardan DT, Meares CF, Goodwin DA et al. Antibodies against metal chelates. Nature316(6025),265–268 (1985).
  • 90  Goodwin DA, Meares CF, David GF et al. Monoclonal antibodies as reversible equilibrium carriers of radiopharmaceuticals. Int. J. Rad. Appl. Instrum. B13(4),383–391 (1986).
  • 91  Hnatowich DJ, Virzi F, Rusckowski M. Investigations of avidin and biotin for imaging applications. J. Nucl. Med.28(8),1294–1302 (1987).
  • 92  Sharkey RM, Karacay H, Cardillo TM et al. Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methods. Clin. Cancer Res.11(19),7109s–7121s (2005).
  • 93  Martensson L, Nilsson R, Ohlsson T, Sjogren HO, Strand SE, Tennvall J. Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy. Clin. Cancer Res.13(18),5572s–5576s (2007).
  • 94  Cai W, Chen K, He L, Cao Q, Koong A, Chen X. Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. Eur. J. Nucl. Med. Mol. Imaging34(6),850–858 (2007).
  • 95  Ping Li W, Meyer LA, Capretto DA, Sherman CD, Anderson CJ. Receptor-binding, biodistribution, and metabolism studies of Cu-64-DOTA-cetuximab, a PET-imaging agent for epidermal growth-factor receptor-positive tumors. Cancer Biother. Radiopharm.23(2),158–171 (2008).
  • 96  Niu G, Li Z, Xie J, Le QT, Chen X. PET of EGFR antibody distribution in head and neck squamous cell carcinoma models. J. Nucl. Med.50(7),1116–1123 (2009).
  • 97  Elsasser-Beile U, Reischl G, Wiehr S et al. PET imaging of prostate cancer xenografts with a highly specific antibody against the prostate-specific membrane antigen. J. Nucl. Med.50(4),606–611 (2009).
  • 98  Niu G, Li ZB, Cao QZ, Chen XY. Monitoring therapeutic response of human ovarian cancer to 17-DMAG by noninvasive PET imaging with Cu-64-DOTA-trastuzumab. Eur. J. Nucl. Med. Mol. Imaging36(9),1510–1519 (2009).
  • 99  Wu AM, Yazaki PJ, Tsai S et al. High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Proc. Natl Acad. Sci. USA97(15),8495–8500 (2000).
  • 100  Li L, Bading J, Yazaki PJ et al. A versatile bifunctional chelate for radiolabeling humanized anti-CEA antibody with In-111 and Cu-64 at either thiol or amino groups: PET imaging of CEA-positive tumors with whole antibodies. Bioconjug. Chem.19(1),89–96 (2008).
  • 101  Philpott GW, Schwarz SW, Anderson CJ et al. RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody. J. Nucl. Med.36(10),1818–1824 (1995).
  • 102  Lovqvist A, Humm JL, Sheikh A et al. PET imaging of (86)Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: comparison between (86)Y and (111)In radiolabels. J. Nucl. Med.42(8),1281–1287 (2001).
  • 103  Nayak TK, Regino CA, Wong KJ et al. PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A’’-DTPA-cetuximab. Eur. J. Nucl. Med. Mol. Imaging37(7),1368–1376 (2010).
  • 104  Nayak TK, Garmestani K, Baidoo KE, Milenic DE, Brechbiel MW. Preparation, biological evaluation, and pharmacokinetics of the human anti-HER1 monoclonal antibody panitumumab labeled with 86Y for quantitative PET of carcinoma. J. Nucl. Med.51(6),942–950 (2010).
  • 105  Schneider DW, Heitner T, Alicke B et al. In vivo biodistribution, PET imaging, and tumor accumulation of 86Y- and 111In-antimindin/RG-1, engineered antibody fragments in LNCaP tumor-bearing nude mice. J. Nucl. Med.50(3),435–443 (2009).
  • 106  Aerts HJ, Dubois L, Perk L et al. Disparity between in vivo EGFR expression and 89Zr-labeled cetuximab uptake assessed with PET. J. Nucl. Med.50(1),123–131 (2009).
  • 107  Holland JP, Divilov V, Bander NH, Smith-Jones PM, Larson SM, Lewis JS. 89Zr-DFO-J591 for immunoPET of prostate-specific membrane antigen expression in vivo.J. Nucl. Med.51(8),1293–1300 (2010).
  • 108  Nagengast WB, de Vries EG, Hospers GA et al. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J. Nucl. Med.48(8),1313–1319 (2007).
  • 109  Borjesson PK, Jauw YW, Boellaard R et al. Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. Clin. Cancer Res.12(7 Pt. 1),2133–2140 (2006).▪ First clinical study of zirconium-89.
  • 110  Borjesson PK, Jauw YW, de Bree R et al. Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients. J. Nucl. Med.50(11),1828–1836 (2009).
  • 111  Dijkers EC, Oude Munnink TH, Kosterink JG et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin. Pharmacol. Ther.87(5),586–592 (2010).
  • 112  Glaus C, Rossin R, Welch MJ, Bao G. In vivo evaluation of (64)Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent. Bioconjug. Chem.21(4),715–722 (2010).
  • 113  Minchin RF, Martin DJ. Nanoparticles for molecular imaging – an overview. Endocrinology151(2),474–481 (2010).
  • 114  Chen K, Li ZB, Wang H, Cai W, Chen X. Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots. Eur. J. Nucl. Med. Mol. Imaging35(12),2235–2244 (2008).
  • 115  Michalet X, Pinaud FF, Bentolila LA et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science307(5709),538–544 (2005).
  • 116  Bruchez M Jr., Moronne M, Gin P, Weiss S, Alivisatos AP. Semiconductor nanocrystals as fluorescent biological labels. Science281(5385),2013–2016 (1998).
  • 117  Chan WC, Nie S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science281(5385),2016–2018 (1998).
  • 118  Cai W, Chen K, Li ZB, Gambhir SS, Chen X. Dual-function probe for PET and near-infrared fluorescence imaging of tumor vasculature. J. Nucl. Med.48(11),1862–1870 (2007).
  • 119  Medintz IL, Uyeda HT, Goldman ER, Mattoussi H. Quantum dot bioconjugates for imaging, labeling and sensing. Nat. Mater.4(6),435–446 (2005).
  • 120  Vuu K, Xie J, McDonald MA et al. Gadolinium-rhodamine nanoparticles for cell labeling and tracking via magnetic resonance and optical imaging. Bioconjug. Chem.16(4),995–999 (2005).
  • 121  van Tilborg GA, Mulder WJ, Deckers N et al. Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis. Bioconjug. Chem.17(3),741–749 (2006).
  • 122  Rieter WJ, Kim JS, Taylor KM, An H, Lin W, Tarrant T. Hybrid silica nanoparticles for multimodal imaging. Angew. Chem. Int. Ed. Engl.46(20),3680–3682 (2007).
  • 123  Kim JS, Rieter WJ, Taylor KM, An H, Lin W. Self-assembled hybrid nanoparticles for cancer-specific multimodal imaging. J. Am. Chem. Soc.129(29),8962–8963 (2007).
  • 124  Islam T, Josephson L. Current state and future applications of active targeting in malignancies using superparamagnetic iron oxide nanoparticles. Cancer Biomark.5(2),99–107 (2009).
  • 125  Josephson L, Kircher MF, Mahmood U, Tang Y, Weissleder R. Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes. Bioconjug. Chem.13(3),554–560 (2002).
  • 126  Jennings LE, Long NJ. ‘Two is better than one’ – probes for dual-modality molecular imaging. Chem. Commun. (Camb.) (24), 3511–3524 (2009).
  • 127  Nahrendorf M, Zhang H, Hembrador S et al. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation117(3),379–387 (2008).
  • 128  Holland JP, Caldas-Lopes E, Divilov V et al. Measuring the pharmacodynamic effects of a novel Hsp90 inhibitor on HER2/neu expression in mice using Zr-DFO-trastuzumab. PLoS One5(1),e8859 (2010).
  • 129  Dijkers EC, Kosterink JG, Rademaker AP et al. Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging. J. Nucl. Med.50(6),974–981 (2009).