Education

Research Areas

Cancer diagnostics, radiopharmaceutical imaging and therapy; cell and molecular imaging; phage display.

Research Description

We have an established research program to develop radiolabeled peptides, proteins and nanoparticles as tumor specific diagnostic and therapeutic agents. Combinatorial peptide and antibody fragment libraries are being employed to identify molecules that preferentially bind tumor antigens. The tumor-avid peptides, antibody fragments and nanoparticles are subsequently engineered to bind the medically important radionuclides into their structures. Finally, the radiolabeled peptides, proteins and nanoparticles are investigated for their abilities to target tumor cells in vitro and in vivo in support of eventual clinical translation.

Radiolabeled Melanoma avid α-MSH Peptide Analogs: The goal of this project is to design radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs for melanoma imaging and therapy. α-MSH is a small tridecapeptide hormone that binds the melanocortin-1 receptor (MC1R) over expressed on melanoma tumor cells. Cyclic α-MSH peptide analogs have been synthesized and radiolabeled with ^99mTc, ¹¹¹In, ⁶⁴Cu and ⁶⁸Ga for melanoma imaging and ¹⁸⁸Re, ¹⁷⁷Lu and ²¹²Pb for melanoma therapy.

Melanoma Targeting Nanoparticles: In collaboration with Memorial Sloan Kettering and Cornell University, cyclic α-MSH analogs have been incorporated into ultrasmall (< 10 nm dia.) silica nanoparticles (C′ dots) for melanoma diagnosis, treatment and image-guided surgery. In pre-clinical melanoma animal models, the ¹²⁴I-α-MSH-C′ dots were shown to imaged melanoma tumors, while in therapy studies ¹⁷⁷Lu-DOTA-α-MSH-C′ dot treatment of melanoma bearing mice demonstrated significantly prolonged survival over control groups. Administration of α-MSH-C′ dots at high concentrations resulted in tumor cell death via a novel ferroptosis mechanism. The first generation of radiolabeled C′ dots for melanoma imaging and image-guided surgery have been translated into the clinic. Additional peptide and single chain antibody fragment (scFv) conjugated C′ dots are in the pipeline.

Tumor Binding Peptides and Antibody Fragments Selected from Bacteriophage Display Libraries: A combinatorial approach is being used to discover small peptides and single chain antibody fragments (scFvs) that bind the cancer associated Thomsen-Friedenreich (TF) glycoantigen, ErbB-2 receptor and matrix-metalloproteinase-12 (MMP-12) with high affinities and specificities from random peptide and scFv bacteriophage display libraries. Peptides that bound the TF and ErbB-2 were radiolabeled with ⁶⁴Cu and used to image tumors in murine breast cancer models. Recently, MMP-12 binding scFvs were radiolabeled with ⁶⁷Ga and shown to bind lung carcinomas. The MMP-12 scFvs were conjugated to the C′ dot nanoparticles, radiolabeled with ⁸⁹Zr and shown to exhibit superior imaging properties to radiolabeled scFv alone.

Honors and Service

• Director, Molecular Interactions Core
• Gamma Sigma Delta teaching award
• University of Missouri Entrepreneur of the Year (2007)

Selected Publications

Li M, Liu D, Lee D, Kapoor S, Gibson-Corley KN, Quinn TP, Sagastume EA, Mott SL, Walsh SA, Acevedo MR, Johnson FL, Schultz MK. (2019). Enhancing the Efficacy of Melanocortin 1 Receptor-Targeted Radiotherapy by Pharmacologically Upregulating the Receptor in Metastatic Melanoma. Mol Pharm. 16(9):3904-3915. doi: 10.1021/acs.molpharmaceut.9b00512. [PubMed]

Singh K, Gallazzi F, Hill KJ, Burke DH, Lange MJ, Quinn TP, Neogi U, Sönnerborg A. (2019). GS-CA Compounds: First-In-Class HIV-1 Capsid Inhibitors Covering Multiple Grounds. Front Microbiol. 10:1227. doi: 10.3389/fmicb.2019.01227. eCollection 2019. [PubMed]

Li M, Zhang X, Quinn TP, Lee D, Liu D, Kunkel F, Zimmerman BE, McAlister D, Olewein K, Menda Y, Mirzadeh S, Copping R, Johnson FL, Schultz MK. (Isot). Corrigendum to “Automated cassette-based production of high specific activity [(203/212)Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer” [Appl. Radiat. Isot. 127 (2017) 52-60]. Appl Radiat Isot. 2019 Jun 12. doi: 10.1016/j.apradiso.2019.05.019. Epub ahead of print. [PubMed]

Chen F, Ma K, Madajewski B, Zhuang L, Zhang L, Rickert K, Marelli M, Yoo B, Turker MZ, Overholtzer M, Quinn TP, Gonen M, Zanzonico P, Tuesca A, Bowen MA, Norton L, Subramony JA, Wiesner U, Bradbury MS. (2018). Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer. Nat Commun. 9(1):4141. doi: 10.1038/s41467-018-06271-5. [PubMed]

Shah MA, Zhang X, Rossin R, Robillard MS, Fisher DR, Bueltmann T, Hoeben FJM, Quinn TP. (2017). Metal-Free Cycloaddition Chemistry Driven Pretargeted Radioimmunotherapy Using α-Particle Radiation. Bioconjug Chem. 28(12):3007-3015. doi: 10.1021/acs.bioconjchem.7b00612. [PubMed]

Chen F, Zhang X, Ma K, Madajewski B, Benezra M, Zhang L, Phillips E, Turker MZ, Gallazzi F, Penate-Medina O, Overholtzer M, Pauliah M, Gonen M, Zanzonico P, Wiesner U, Bradbury MS, Quinn TP. (2018). Melanocortin-1 Receptor-Targeting Ultrasmall Silica Nanoparticles for Dual-Modality Human Melanoma Imaging. ACS Appl Mater Interfaces. 10(5):4379-4393. doi: 10.1021/acsami.7b14362. Erratum in: ACS Appl Mater Interfaces. 2018 Oct 24;10(42):36584. [PubMed]

Li M, Zhang X, Quinn TP, Lee D, Liu D, Kunkel F, Zimmerman BE, McAlister D, Olewein K, Menda Y, Mirzadeh S, Copping R, Johnson FL, Schultz MK. (2017). Automated cassette-based production of high specific activity [(203/212)Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer. Appl Radiat Isot. 127:52-60. doi: 10.1016/j.apradiso.2017.05.006. Erratum in: Appl Radiat Isot. 2019 Jun 12;:. [PubMed]

Teixeira V, Fernández M, Oddone N, Zhang X, Gallazzi F, Cerecetto H, Gambini JP, Porcal W, Cabral P, Quinn TP. (2017). The Effect of A Hexanoic Acid Linker Insertion on the Pharmacokinetics and Tumor Targeting Properties of the Melanoma Imaging Agent 99mTc-HYNIC-cycMSH. Anticancer Agents Med Chem. 17(8):1144-1152. doi: 10.2174/1871520616666161206144414. [PubMed]

Kirby KA, Ong YT, Hachiya A, Laughlin TG, Chiang LA, Pan Y, Moran JL, Marchand B, Singh K, Gallazzi F, Quinn TP, Yoshimura K, Murakami T, Matsushita S, Sarafianos SG. (2015). Structural basis of clade-specific HIV-1 neutralization by humanized anti-V3 monoclonal antibody KD-247. FASEB J. 29(1):70-80. doi: 10.1096/fj.14-252262. [PubMed]

Zhang X, Teixeira V, Porcal W, Cabral P, Gambini JP, Fernandez M, Gallazzi F, Quinn TP. (2014). [99mTc(CO)3]+ and [99mTcO2]+ radiolabeled cyclic melanotropin peptides for melanoma SPECT imaging. Curr Radiopharm. 7(1):63-74. [PubMed]