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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

The Influence of Different Spacers on Biological Profile of Peptide Radiopharmaceuticals for Diagnosis and Therapy of Human Cancers

Author(s): Arezou M. Farahani, Fariba Maleki and Nourollah Sadeghzadeh*

Volume 20 , Issue 4 , 2020

Page: [402 - 416] Pages: 15

DOI: 10.2174/1871520620666191231161227

Price: $65


Background: Cancer is the leading cause of death worldwide. Early detection can reduce the disadvantageous effects of diseases and the mortality in cancer. Nuclear medicine is a powerful tool that has the ability to diagnose malignancy without harming normal tissues. In recent years, radiolabeled peptides have been investigated as potent agents for cancer detection. Therefore, it is necessary to modify radiopeptides in order to achieve more effective agents.

Objective: This review describes modifications in the structure of radioconjugates with spacers who have improved the specificity and sensitivity of the peptides that are used in oncologic diagnosis and therapy.

Methods: To improve the biological activity, researchers have conjugated these peptide analogs to different spacers and bifunctional chelators. Many spacers of different kinds, such as hydrocarbon chain, amino acid sequence, and poly (ethyleneglycol) were introduced in order to modify the pharmacokinetic properties of these biomolecules.

Results: Different spacers have been applied to develop radiolabeled peptides as potential tracers in nuclear medicine. Spacers with different charge and hydrophilicity affect the characteristics of peptide conjugate. For example, the complex with uncharged and hydrophobic spacers leads to increased liver uptake, while the composition with positively charged spacers results in high kidney retention. Therefore, the pharmacokinetics of radio complexes correlates to the structure and total charge of the conjugates.

Conclusion: Radio imaging technology has been successfully applied to detect a tumor in the earliest stage. For this purpose, the assessment of useful agents to diagnose the lesion is necessary. Developing peptide radiopharmaceuticals using spacers can improve in vitro and in vivo behavior of radiotracers leading to better noninvasive detection and monitoring of tumor growth.

Keywords: Radiolabeled peptide, cancer, spacer, nuclear medicine, cancer detection, oncologic diagnosis.

Graphical Abstract
Rezazadeh, F.; Sadeghzadeh, N. Tumor targeting with 99m Tc radiolabeled peptides: Clinical application and recent development. Chem. Biol. Drug Des., 2019, 93(1), 205-221.
[] [PMID: 30299570]
Laverman, P.; Sosabowski, J.K.; Boerman, O.C.; Oyen, W.J. Radiolabelled peptides for oncological diagnosis. Eur. J. Nucl. Med. Mol. Imaging, 2012, 39(1)(Suppl. 1), S78-S92.
[] [PMID: 22388627]
Okarvi, S.M. Peptide-based radiopharmaceuticals and cytotoxic conjugates: potential tools against cancer. Cancer Treat. Rev., 2008, 34(1), 13-26.
[] [PMID: 17870245]
Jamous, M.; Tamma, M.L.; Gourni, E.; Waser, B.; Reubi, J.C.; Maecke, H.R.; Mansi, R. PEG spacers of different length influence the biological profile of bombesin-based radiolabeled antagonists. Nucl. Med. Biol., 2014, 41(6), 464-470.
[] [PMID: 24780298]
Fani, M.; Maecke, H.R.; Okarvi, S.M. Radiolabeled peptides: valuable tools for the detection and treatment of cancer. Theranostics, 2012, 2(5), 481-501.
[] [PMID: 22737187]
Prasanphanich, A.F.; Lane, S.R.; Figueroa, S.D.; Ma, L.; Rold, T.L.; Sieckman, G.L.; Hoffman, T.J.; McCrate, J.M.; Smith, C.J. The effects of linking substituents on the in vivo behavior of site-directed, peptide-based, diagnostic radiopharmaceuticals. In Vivo, 2007, 21(1), 1-16.
[PMID: 17354608]
Däpp, S.; García Garayoa, E.; Maes, V.; Brans, L.; Tourwé, D.A.; Müller, C.; Schibli, R. PEGylation of (99m)Tc-labeled bombesin analogues improves their pharmacokinetic properties. Nucl. Med. Biol., 2011, 38(7), 997-1009.
[] [PMID: 21982571]
Liu, S. Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides. Adv. Drug Deliv. Rev., 2008, 60(12), 1347-1370.
[] [PMID: 18538888]
Guo, H.; Hathaway, H.; Royce, M.E.; Prossnitz, E.R.; Miao, Y. Influences of hydrocarbon linkers on the receptor binding affinities of gonadotropin-releasing hormone peptides. Bioorg. Med. Chem. Lett., 2013, 23(20), 5484-5487.
[] [PMID: 24018188]
Reubi, J.C.; Wenger, S.; Schmuckli-Maurer, J.; Schaer, J-C.; 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., 2002, 8(4), 1139-1146.
[PMID: 11948125]
Smith, C.J.; Sieckman, G.L.; Owen, N.K.; Hayes, D.L.; Mazuru, D.G.; Kannan, R.; Volkert, W.A.; Hoffman, T.J. Radiochemical investigations of gastrin-releasing peptide receptor-specific [(99m)Tc(X)(CO)3-Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH2)] in PC-3, tumor-bearing, rodent models: syntheses, radiolabeling, and in vitro/in vivo studies where Dpr = 2,3-diaminopropionic acid and X = H2O or P(CH2OH)3. Cancer Res., 2003, 63(14), 4082-4088.
[PMID: 12874010]
Alves, S.; Correia, J.D.; Santos, I.; Veerendra, B.; Sieckman, G.L.; Hoffman, T.J.; Rold, T.L.; Figueroa, S.D.; Retzloff, L.; McCrate, J.; Prasanphanich, A.; Smith, C.J. Pyrazolyl conjugates of bombesin: a new tridentate ligand framework for the stabilization of fac-[M(CO)3]+ moiety. Nucl. Med. Biol., 2006, 33(5), 625-634.
[] [PMID: 16843837]
Sancho, V.; Di Florio, A.; Moody, T.W.; Jensen, R.T. Bombesin receptor-mediated imaging and cytotoxicity: review and current status. Curr. Drug Deliv., 2011, 8(1), 79-134.
[] [PMID: 21034419]
Parry, J.J.; Andrews, R.; Rogers, B.E. MicroPET imaging of breast cancer using radiolabeled bombesin analogs targeting the gastrin-releasing peptide receptor. Breast Cancer Res. Treat., 2007, 101(2), 175-183.
[] [PMID: 16838112]
Parry, J.J.; Kelly, T.S.; Andrews, R.; Rogers, B.E. In vitro and in vivo evaluation of 64Cu-labeled DOTA-linker-bombesin(7-14) analogues containing different amino acid linker moieties. Bioconjug. Chem., 2007, 18(4), 1110-1117.
[] [PMID: 17503761]
Kunstler, J.U.; Veerendra, B.; Figueroa, S.D.; Sieckman, G.L.; Rold, T.L.; Hoffman, T.J.; Smith, C.J.; Pietzsch, H.J. Organometallic 99mTc(III) ‘4 + 1’ bombesin(7-14) conjugates: synthesis, radiolabeling, and in vitro/in vivo studies. Bioconjug. Chem., 2007, 18(5), 1651-1661.
[] [PMID: 17663527]
Lane, S.R.; Veerendra, B.; Rold, T.L.; Sieckman, G.L.; Hoffman, T.J.; Jurisson, S.S.; Smith, C.J. 99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GRP receptor. Nucl. Med. Biol., 2008, 35(3), 263-272.
[] [PMID: 18355681]
Retzloff, L.B.; Heinzke, L.; Figureoa, S.D.; Sublett, S.V.; Ma, L.; Sieckman, G.L.; Rold, T.L.; Santos, I.; Hoffman, T.J.; Smith, C.J. Evaluation of [99mTc-(CO)3-X-Y-Bombesin(7-14)NH2] conjugates for targeting gastrin-releasing peptide receptors overexpressed on breast carcinoma. Anticancer Res., 2010, 30(1), 19-30.
[PMID: 20150613]
García Garayoa, E.; Rüegg, D.; Bläuenstein, P.; Zwimpfer, M.; Khan, I.U.; Maes, V.; Blanc, A.; Beck-Sickinger, A.G.; Tourwé, D.A.; Schubiger, P.A. Chemical and biological characterization of new Re(CO)3/[99mTc](CO)3 bombesin analogues. Nucl. Med. Biol., 2007, 34(1), 17-28.
[] [PMID: 17210458]
García Garayoa, E.; Schweinsberg, C.; Maes, V.; Brans, L.; Bläuenstein, P.; Tourwé, D.A.; Schibli, R.; Schubiger, P.A. Influence of the molecular charge on the biodistribution of bombesin analogues labeled with the [99mTc(CO)3]-core. Bioconjug. Chem., 2008, 19(12), 2409-2416.
[] [PMID: 18998719]
Schweinsberg, C.; Maes, V.; Brans, L.; Bläuenstein, P.; Tourwé, D.A.; Schubiger, P.A.; Schibli, R.; García, G.E. Novel glycated [99mTc(CO)3]-labeled bombesin analogues for improved targeting of gastrin-releasing peptide receptor-positive tumors. Bioconjug. Chem., 2008, 19(12), 2432-2439.
[] [PMID: 19053304]
Fragogeorgi, E.A.; Zikos, C.; Gourni, E.; Bouziotis, P.; Paravatou-Petsotas, M.; Loudos, G.; Mitsokapas, N.; Xanthopoulos, S.; Mavri-Vavayanni, M.; Livaniou, E.; Varvarigou, A.D.; Archimandritis, S.C. Spacer site modifications for the improvement of the in vitro and in vivo binding properties of (99m)Tc-N(3)S-X-bombesin[2-14] derivatives. Bioconjug. Chem., 2009, 20(5), 856-867.
[] [PMID: 19344122]
Liolios, C.C.; Fragogeorgi, E.A.; Zikos, C.; Loudos, G.; Xanthopoulos, S.; Bouziotis, P.; Paravatou-Petsotas, M.; Livaniou, E.; Varvarigou, A.D.; Sivolapenko, G.B. Structural modifications of 99mTc-labelled bombesin-like peptides for optimizing pharmacokinetics in prostate tumor targeting. Int. J. Pharm., 2012, 430(1-2), 1-17.
[] [PMID: 22459664]
Smith, C.J.; Gali, H.; Sieckman, G.L.; Higginbotham, C.; Volkert, W.A.; Hoffman, T.J. Radiochemical investigations of (99m)Tc-N(3)S-X-BBN[7-14]NH(2): an in vitro/in vivo structure-activity relationship study where X = 0-, 3-, 5-, 8-, and 11-carbon tethering moieties. Bioconjug. Chem., 2003, 14(1), 93-102.
[] [PMID: 12526698]
Hoffman, T.; Simpson, S.; Smith, C.; Simmons, J.; Sieckman, G.; Higginbotham, C.; Eshima, D.; Volkert, W.; Thornback, J. Accumulation and retention of Tc-99m RP527 by GRP receptor expressing tumors in scid mice. J. Nucl. Med., 1999, 40(Suppl.), 104.
Carlucci, G.; Ananias, H.J.; Yu, Z.; Hoving, H.D.; Helfrich, W.; Dierckx, R.A.; Liu, S.; de Jong, I.J.; Elsinga, P.H. Preclinical evaluation of a novel 111In-labeled bombesin homodimer for improved imaging of GRPR-positive prostate cancer. Mol. Pharm., 2013, 10(5), 1716-1724.
[] [PMID: 23590837]
Hoffman, T.J.; Gali, H.; Smith, C.J.; Sieckman, G.L.; Hayes, D.L.; Owen, N.K.; Volkert, W.A. Novel series of 111In-labeled bombesin analogs as potential radiopharmaceuticals for specific targeting of gastrin-releasing peptide receptors expressed on human prostate cancer cells. J. Nucl. Med., 2003, 44(5), 823-831.
[PMID: 12732685]
Garrison, J.C.; Rold, T.L.; Sieckman, G.L.; Naz, F.; Sublett, S.V.; Figueroa, S.D.; Volkert, W.A.; Hoffman, T.J. Evaluation of the pharmacokinetic effects of various linking group using the 111In-DOTA-X-BBN(7-14)NH2 structural paradigm in a prostate cancer model. Bioconjug. Chem., 2008, 19(9), 1803-1812.
[] [PMID: 18712899]
La Bella, R.; Garcia-Garayoa, E.; Langer, M.; Bläuenstein, P.; Beck-Sickinger, A.G.; Schubiger, P.A. In vitro and in vivo evaluation of a 99mTc(I)-labeled bombesin analogue for imaging of gastrin releasing peptide receptor-positive tumors. Nucl. Med. Biol., 2002, 29(5), 553-560.
[] [PMID: 12088725]
La Bella, R.; Garcia-Garayoa, E.; Bähler, M.; Bläuenstein, P.; Schibli, R.; Conrath, P.; Tourwé, D.; Schubiger, P.A. A 99mTc(I)-postlabeled high affinity bombesin analogue as a potential tumor imaging agent. Bioconjug. Chem., 2002, 13(3), 599-604.
[] [PMID: 12009951]
Smith, C.J.; Hoffman, T.J.; Hayes, D.L.; Owen, N.K.; Sieckman, G.L.; Volkert, W.A. Radiochemical investigations of 177Lu‐DOTA‐8‐Aoc‐BBN [7‐14] NH2: A new gastrin releasing peptide receptor (GRPr) targeting radiopharma ceutical. J. Labelled Comp. Radiopharm., 2001, 44(S1), S706-S708.
Rogers, B.E.; Bigott, H.M.; McCarthy, D.W.; Della Manna, D.; Kim, J.; Sharp, T.L.; Welch, M.J. MicroPET imaging of a gastrin-releasing peptide receptor-positive tumor in a mouse model of human prostate cancer using a 64Cu-labeled bombesin analogue. Bioconjug. Chem., 2003, 14(4), 756-763.
[] [PMID: 12862428]
Rogers, B.E.; Manna, D.D.; Safavy, A. In vitro and in vivo evaluation of a 64Cu-labeled polyethylene glycol-bombesin conjugate. Cancer Biother. Radiopharm., 2004, 19(1), 25-34.
[] [PMID: 15068608]
Dimitrakopoulou-Strauss, A.; Hohenberger, P.; Haberkorn, U.; Mäcke, H.R.; Eisenhut, M.; Strauss, L.G. 68Ga-labeled bombesin studies in patients with gastrointestinal stromal tumors: comparison with 18F-FDG. J. Nucl. Med., 2007, 48(8), 1245-1250.
[] [PMID: 17631559]
Van de Wiele, C.; Phonteyne, P.; Pauwels, P.; Goethals, I.; Van den Broecke, R.; Cocquyt, V.; Dierckx, R.A. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry. J. Nucl. Med., 2008, 49(2), 260-264.
[] [PMID: 18199617]
García Garayoa, E.; Schweinsberg, C.; Maes, V.; Rüegg, D.; Blanc, A.; Bläuenstein, P.; Tourwé, D.A.; Beck-Sickinger, A.G.; Schubiger, P.A. New [99mTc]bombesin analogues with improved biodistribution for targeting gastrin releasing-peptide receptor-positive tumors. Q. J. Nucl. Med. Mol. Imaging, 2007, 51(1), 42-50.
[PMID: 17372572]
Abiraj, K.; Mansi, R.; Tamma, M-L.; Fani, M.; Forrer, F.; Nicolas, G.; Cescato, R.; Reubi, J.C.; Maecke, H.R. Bombesin antagonist-based radioligands for translational nuclear imaging of gastrin-releasing peptide receptor-positive tumors. J. Nucl. Med., 2011, 52(12), 1970-1978.
[] [PMID: 22080443]
Däpp, S.; Müller, C.; Garayoa, E.G.; Bläuenstein, P.; Maes, V.; Brans, L.; Tourwé, D.A.; Schibli, R. PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues. EJNMMI Res., 2012, 2(1), 24.
[] [PMID: 22681935]
Varasteh, Z.; Velikyan, I.; Lindeberg, G.; Sörensen, J.; Larhed, M.; Sandström, M.; Selvaraju, R.K.; Malmberg, J.; Tolmachev, V.; Orlova, A. Synthesis and characterization of a high-affinity NOTA-conjugated bombesin antagonist for GRPR-targeted tumor imaging. Bioconjug. Chem., 2013, 24(7), 1144-1153.
[] [PMID: 23763444]
Varasteh, Z.; Rosenström, U.; Velikyan, I.; Mitran, B.; Altai, M.; Honarvar, H.; Rosestedt, M.; Lindeberg, G.; Sörensen, J.; Larhed, M.; Tolmachev, V.; Orlova, A. The effect of mini-PEG-based spacer length on binding and pharmacokinetic properties of a 68Ga-labeled NOTA-conjugated antagonistic analog of bombesin. Molecules, 2014, 19(7), 10455-10472.
[] [PMID: 25036155]
Varasteh, Z.; Åberg, O.; Velikyan, I.; Lindeberg, G.; Sörensen, J.; Larhed, M.; Antoni, G.; Sandström, M.; Tolmachev, V.; Orlova, A. In vitro and in vivo evaluation of a (18)F-labeled high affinity NOTA conjugated bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging. PLoS One, 2013, 8(12) e81932
[] [PMID: 24312607]
Zhang, H.; Schuhmacher, J.; Waser, B.; Wild, D.; Eisenhut, M.; Reubi, J.C.; Maecke, H.R. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours. Eur. J. Nucl. Med. Mol. Imaging, 2007, 34(8), 1198-1208.
[] [PMID: 17262215]
Mansi, R.; Wang, X.; Forrer, F.; Kneifel, S.; Tamma, M-L.; Waser, B.; Cescato, R.; Reubi, J.C.; Maecke, H.R. Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides. Clin. Cancer Res., 2009, 15(16), 5240-5249.
[] [PMID: 19671861]
Mansi, R.; Wang, X.; Forrer, F.; Waser, B.; Cescato, R.; Graham, K.; Borkowski, S.; Reubi, J.C.; Maecke, H.R. Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38(1), 97-107.
[] [PMID: 20717822]
Liu, S. Radiolabeled cyclic RGD peptides as integrin α(v)β(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug. Chem., 2009, 20(12), 2199-2213.
[] [PMID: 19719118]
Dijkgraaf, I.; Liu, S.; Kruijtzer, J.A.; Soede, A.C.; Oyen, W.J.; Liskamp, R.M.; Corstens, F.H.; Boerman, O.C. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide. Nucl. Med. Biol., 2007, 34(1), 29-35.
[] [PMID: 17210459]
Jia, B.; Liu, Z.; Shi, J.; Yu, Z.; Yang, Z.; Zhao, H.; He, Z.; Liu, S.; Wang, F. Linker effects on biological properties of 111In-labeled DTPA conjugates of a cyclic RGDfK dimer. Bioconjug. Chem., 2008, 19(1), 201-210.
[] [PMID: 18069778]
Chen, X.; Park, R.; Shahinian, A.H.; Bading, J.R.; Conti, P.S. Pharmacokinetics and tumor retention of 125I-labeled RGD peptide are improved by PEGylation. Nucl. Med. Biol., 2004, 31(1), 11-19.
[] [PMID: 14741566]
Liu, S. The role of coordination chemistry in the development of target-specific radiopharmaceuticals. Chem. Soc. Rev., 2004, 33(7), 445-461.
[] [PMID: 15354226]
Poethko, T.; Thumshirn, G.; Hersel, U.; Rau, F.; Haubner, R.; Schwaiger, M.; Kessler, H.; Wester, H. Improved tumor uptake, tumor retention and tumor/background ratios of pegylated RGD-multimers. J. Nucl. Med., 2003, 44.
Liu, S.; He, Z.; Hsieh, W-Y.; Kim, Y-S.; Jiang, Y. Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer. Bioconjug. Chem., 2006, 17(6), 1499-1507.
[] [PMID: 17105229]
Wang, L.; Shi, J.; Kim, Y-S.; Zhai, S.; Jia, B.; Zhao, H.; Liu, Z.; Wang, F.; Chen, X.; Liu, S. Improving tumor-targeting capability and pharmacokinetics of (99m)Tc-labeled cyclic RGD dimers with PEG(4) linkers. Mol. Pharm., 2009, 6(1), 231-245.
[] [PMID: 19067525]
Shi, J.; Kim, Y-S.; Zhai, S.; Liu, Z.; Chen, X.; Liu, S. Improving tumor uptake and pharmacokinetics of (64)Cu-labeled cyclic RGD peptide dimers with Gly(3) and PEG(4) linkers. Bioconjug. Chem., 2009, 20(4), 750-759.
[] [PMID: 19320477]
Chen, X.; Park, R.; Hou, Y.; Khankaldyyan, V.; Gonzales-Gomez, I.; Tohme, M.; Bading, J.R.; Laug, W.E.; Conti, P.S. MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide. Eur. J. Nucl. Med. Mol. Imaging, 2004, 31(8), 1081-1089.
[] [PMID: 15118844]
Wu, Z.; Li, Z-B.; Cai, W.; He, L.; Chin, F.T.; Li, F.; Chen, X. 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of alphavbeta3 integrin expression. Eur. J. Nucl. Med. Mol. Imaging, 2007, 34(11), 1823-1831.
[] [PMID: 17492285]
Liu, Z.; Liu, S.; Wang, F.; Liu, S.; Chen, X. Noninvasive imaging of tumor integrin expression using (18)F-labeled RGD dimer peptide with PEG (4) linkers. Eur. J. Nucl. Med. Mol. Imaging, 2009, 36(8), 1296-1307.
[] [PMID: 19296102]
Guo, H.; Shenoy, N.; Gershman, B.M.; Yang, J.; Sklar, L.A.; Miao, Y. Metastatic melanoma imaging with an (111)In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptide. Nucl. Med. Biol., 2009, 36(3), 267-276.
[] [PMID: 19324272]
Miao, Y.; Benwell, K.; Quinn, T.P. 99mTc- and 111In-labeled α-melanocyte-stimulating hormone peptides as imaging probes for primary and pulmonary metastatic melanoma detection. J. Nucl. Med., 2007, 48(1), 73-80.
[PMID: 17204701]
Miao, Y.; Gallazzi, F.; Guo, H.; Quinn, T.P. 111In-labeled lactam bridge-cyclized α-melanocyte stimulating hormone peptide analogues for melanoma imaging. Bioconjug. Chem., 2008, 19(2), 539-547.
[] [PMID: 18197608]
Guo, H.; Yang, J.; Gallazzi, F.; Miao, Y. Effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of 111In-labeled lactam bridge-cyclized α-MSH peptides. J. Nucl. Med., 2011, 52(4), 608-616.
[] [PMID: 21421725]
Guo, H.; Miao, Y. Introduction of an 8-aminooctanoic acid linker enhances uptake of 99mTc-labeled lactam bridge-cyclized α-MSH peptide in melanoma. J. Nucl. Med., 2014, 55(12), 2057-2063.
[] [PMID: 25453052]
Shamshirian, D.; Erfani, M.; Beiki, D.; Fallahi, B.; Shafiei, M. Development of a (99m)Tc-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors. Ann. Nucl. Med., 2015, 29(8), 709-720.
[] [PMID: 26152564]
Guo, H.; Gallazzi, F.; Miao, Y. Design and evaluation of new Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptides for melanoma imaging. Mol. Pharm., 2013, 10(4), 1400-1408.
[] [PMID: 23418722]
Cheng, Z.; Chen, J.; Quinn, T.P.; Jurisson, S.S. Radioiodination of rhenium cyclized α-melanocyte-stimulating hormone resulting in enhanced radioactivity localization and retention in melanoma. Cancer Res., 2004, 64(4), 1411-1418.
[] [PMID: 14973076]
Guo, H.; Gallazzi, F.; Sklar, L.A.; Miao, Y. A novel indium-111-labeled gonadotropin-releasing hormone peptide for human prostate cancer imaging. Bioorg. Med. Chem. Lett., 2011, 21(18), 5184-5187.
[] [PMID: 21821417]
Guo, H.; Lu, J.; Hathaway, H.; Royce, M.E.; Prossnitz, E.R.; Miao, Y. Synthesis and evaluation of novel gonadotropin-releasing hormone receptor-targeting peptides. Bioconjug. Chem., 2011, 22(8), 1682-1689.
[] [PMID: 21749045]
Xu, J.; Feng, C.; Miao, Y. Evaluation of novel 111In-labeled gonadotropin-releasing hormone peptides for human prostate cancer imaging. Bioorg. Med. Chem. Lett., 2017, 27(20), 4647-4651.
[] [PMID: 28917649]
Teodoro, R.; Faintuch, B.L.; Núñez, E.G.F.; Queiróz, R.G. Neurotensin(8-13) analogue: radiolabeling and biological evaluation using different chelators. Nucl. Med. Biol., 2011, 38(1), 113-120.
[] [PMID: 21220134]
Jia, Y.; Shi, W.; Zhou, Z.; Wagh, N.K.; Fan, W.; Brusnahan, S.K.; Garrison, J.C. Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting. Nucl. Med. Biol., 2015, 42(11), 816-823.
[] [PMID: 26302836]
De, K.; Behera, A.; Banerjee, I.; Sarkar, B.; Ganguly, S.; Misra, M. Radiolabeled novel peptide for imaging somatostatin-receptor expressing tumor: Synthesis and radiobiological evaluation. J. Radioanal. Nucl. Chem., 2014, 301(3), 847-861.
Antunes, P.; Ginj, M.; Walter, M.A.; Chen, J.; Reubi, J-C.; Maecke, H.R. Influence of different spacers on the biological profile of a DOTA-somatostatin analogue. Bioconjug. Chem., 2007, 18(1), 84-92.
[] [PMID: 17226960]
Kolenc-Peitl, P.; Mansi, R.; Tamma, M.; Gmeiner-Stopar, T.; Sollner-Dolenc, M.; Waser, B.; Baum, R.P.; Reubi, J.C.; Maecke, H.R. Highly improved metabolic stability and pharmacokinetics of indium-111-DOTA-gastrin conjugates for targeting of the gastrin receptor. J. Med. Chem., 2011, 54(8), 2602-2609.
[] [PMID: 21456601]
Leriche, G.; Chisholm, L.; Wagner, A. Cleavable linkers in chemical biology. Bioorg. Med. Chem., 2012, 20(2), 571-582.
[] [PMID: 21880494]
Uehara, T.; Rokugawa, T.; Kinoshita, M.; Nemoto, S.; Fransisco Lazaro, G.G.; Hanaoka, H.; Arano, Y. (67/68)Ga-labeling agent that liberates (67/68)Ga-NOTA-methionine by lysosomal proteolysis of parental low molecular weight polypeptides to reduce renal radioactivity levels. Bioconjug. Chem., 2014, 25(11), 2038-2045.
[] [PMID: 25303645]
Jodal, A.; Pape, F.; Becker-Pauly, C.; Maas, O.; Schibli, R.; Béhé, M. Evaluation of 111in-labelled exendin-4 derivatives containing different meprin β-specific cleavable linkers. PLoS One, 2015, 10(4) e0123443
[] [PMID: 25855967]

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