title: The inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach.
abstract: In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. (99m)Tc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10(-11)M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), that the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 min to bind more tilmanocept (acting as intracellular "drug compilers" of tilmanocept into non-degraded vesicles), gives serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate (99m)Tc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for imaging approaches. Beyond the elements of imaging applications of these agents is their evolution to therapeutic agents as well, and even in the neo-logical realm of theranostics. Characteristics of agents such as tilmanocept that exploit the natural history of diseases with remarkably high specificity are the expectations for the future of patient- and disease-centered diagnosis and therapy.
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017. Electronic address: fcope@navidea.com.
authors.forename: Frederick O
authors.initials: FO
authors.lastname: Cope
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Abbruzzese
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: James
authors.initials: J
authors.lastname: Sanders
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Wendy
authors.initials: W
authors.lastname: Metz
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Kristyn
authors.initials: K
authors.lastname: Sturms
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: David
authors.initials: D
authors.lastname: Ralph
authors.affiliation: Navidea Biopharmaceuticals, Drug Development, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Michael
authors.initials: M
authors.lastname: Blue
authors.affiliation: The University of California San Francisco and the San Francisco General Hospital, AIDS and Cancer Specimen Resource Center, The Department of Pathology, 1001 Potrero Ave, Bldg. 3, Rm 207 San Francisco, CA 94110.
authors.forename: Jane
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The University of California San Francisco and the San Francisco General Hospital, AIDS and Cancer Specimen Resource Center, The Department of Pathology, 1001 Potrero Ave, Bldg. 3, Rm 207 San Francisco, CA 94110.
authors.forename: Paige
authors.initials: P
authors.lastname: Bracci
authors.affiliation: Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.
authors.forename: Wiam
authors.initials: W
authors.lastname: Bshara
authors.affiliation: Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.
authors.forename: Spencer
authors.initials: S
authors.lastname: Behr
authors.affiliation: Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.
authors.forename: Toby
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Boston College, Department of Biology, 14 Commonwealth Ave, Chestnut Hill, Massachusetts 02467.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Williams
authors.affiliation: Boston College, Department of Biology, 14 Commonwealth Ave, Chestnut Hill, Massachusetts 02467.
authors.forename: Joshua
authors.initials: J
authors.lastname: Walker
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Allison
authors.initials: A
authors.lastname: Beverly
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Brooke
authors.initials: B
authors.lastname: Blay
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Anirudh
authors.initials: A
authors.lastname: Damughatla
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Mark
authors.initials: M
authors.lastname: Larsen
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Courtney
authors.initials: C
authors.lastname: Mountain
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Erin
authors.initials: E
authors.lastname: Neylon
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Kaeli
authors.initials: K
authors.lastname: Parcel
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Kapil
authors.initials: K
authors.lastname: Raghuraman
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ricks
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Lucas
authors.initials: L
authors.lastname: Rose
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Sivakumar
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Streck
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Bryan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wasco
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
authors.forename: Abul
authors.initials: A
authors.lastname: Azad
authors.forename: Murugesan V S
authors.initials: MVS
authors.lastname: Rajaram
authors.forename: Wael
authors.initials: W
authors.lastname: Jarjour
authors.forename: Nicholas
authors.initials: N
authors.lastname: Young
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosol
authors.affiliation: Navidea Biopharmaceuticals Drug Development Internship Program, 5600 Blazer Parkway, Dublin, OH 43017.
authors.forename: Amifred
authors.initials: A
authors.lastname: Williams
authors.affiliation: The University of California San Francisco and the San Francisco General Hospital, AIDS and Cancer Specimen Resource Center, The Department of Pathology, 1001 Potrero Ave, Bldg. 3, Rm 207 San Francisco, CA 94110.
authors.forename: Michael
authors.initials: M
authors.lastname: McGrath
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D012514:Sarcoma, Kaposi / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology / Q000628:therapy
keywords: CD206; Imaging; Immunodiagnostic; Immunotherapy; Macrophage; Tilmanocept