The Steven Larson Lab: Research Overview

The Steven Larson Lab: Research Overview


My laboratory’s primary expertise is in molecular imaging, targeted radio diagnosis, and therapy using small molecules and monoclonal antibodies.

Currently, I am corresponding primary investigator of Memorial Sloan Ketterings’s In Vivo Cellular and Molecular Imaging Center (ICMIC) and coleader, with Ingo Mellinghoff and Charles Sawyers, of Research Project 4, studying molecular imaging correlates and biology of activation of the AR-axis in castrate-resistant prostate cancer. This project builds on extensive prior imaging collaborations with prostate cancer specialists Howard Scher, Michael Morris, and Peter Scardino and has led to the development of molecular imaging approaches to androgen receptor (AR) imaging as well as several novel radioantibodies that image downstream effectors of AR signaling.

My other collaborators include James Fagin, Alan Ho, and Mike Tuttle in the thyroid cancer program; Nai-Kong Cheung, Michel Sadelain, and Jedd Wolchok in cancer immunology; Jorge Carrasquillo, Joseph Osborne, Neeta Pandit-Taskar, and Wolfgang Weber in the Molecular Imaging and Therapy Service; Joe O’Donoghue, John Humm, and Pat Zanzonico in medical physics; and Sarah Cheal, David Ulmert, Darren Veach, and Kishore Pillarsetty in my own lab.

Facilities and Resources

Positron Emission Tomography

Positron emission tomography, often characterized as “metabolic” or “functional” imaging, is a 3D high-resolution imaging modality, which noninvasively provides absolute quantitative measurement of radiotracer concentrations in vivo. Using the appropriate positron-emitting radiotracer in conjunction with blood time-activity measurements and compartmental and other mathematical models, PET can yield measurements of important biochemical and metabolic parameters either regionally (in the form of parametric images) or globally (as average values in whole tumors or individual organs).

Parameters that can be noninvasively measured with PET include blood flow, blood volume, rates of glucose metabolism, protein synthesis or DNA synthesis, receptor or antigen concentrations, and hypoxia. A state-of the-art whole-body PET scanner, the General Electric Advance, is available through the Nuclear Medicine Service of Memorial Hospital. Near-term installation of a second clinical PET scanner is planned. An ultra-high-resolution microPET scanner for imaging small animals (Concorde Microsystems, Inc.) is scheduled for installation in the Nuclear Medicine Laboratory and will be one of only a few such instruments in the world. The microPET consists of four detection rings with a total of 6,144 LSO detector elements (2 x 2 x 10 mm each); with an axial field of view of 8 cm; an animal port diameter of 12 cm; an energy resolution (FWHM) of 19 percent; a timing window (FWHM) of 2.4 ns; and an intrinsic spatial resolution of 1.7 mm.

Radiochemistry and Cyclotron Facility

The Nuclear Medicine Research Laboratory is actively supported by the Radiochemistry and Cyclotron Facility, which routinely produces positron-emitting radionuclides (such as carbon-11, fluorine-18, and iodine-124) and develops and performs organic syntheses of both single-photon-emitting as well as positron-emitting radiotracers, as listed below.

The current cyclotron (Model CS-15, Cyclotron Corp), installed in 1967, is one of the earliest hospital-based cyclotrons in the world and will be replaced within one to two years by a new dual-beam instrument (Model TR19/9, Ebco Technologies).

A Partial List of Precursors and Radiopharmaceuticals (i.e., Materials Prepared in a Form Suitable for Parenteral Administration to Humans) Available through the MSKCC Radiochemistry and Cyclotron Facility.

Other Resources and Facilities

  • Seven large field-of-view dual-detector gamma cameras for static, dynamic, whole-body, and single-photon emission computed tomography (SPECT) imaging of single photon-emitting radiotracers — interfaced with multiple Sun UNIX workstations and networked to an online jukebox optical disk archive
  • Two multichannel analyzer (MCA)-interfaced sodium iodide scintillation probes for measurement of total-body and partial-body activities
  • Three automated sodium iodide scintillation well counters (LKB)
  • A cryostatic microtome
  • A PC-interfaced phosphor plate digital autoradiography imager (BioRad, Model G-350)
  • A PC-interfaced digital microscopy system with computer-driven slide stage for high-power images of large fields of view (Olympus)
  • A fluorescence oxygen probe for determination of tissue oxygen concentrations (at pO2 of 0 to 15 mm) in situ, based on measurement of the O2-quenched lifetime of a luminophor at the tip of a 230-mm diameter optical fiber (OxyLite, Model 400)
  • A dual-pump HPLC system (with a flow-thru scintillation detector) for radiochemical analyses of metabolites, etc. (Waters)
  • A cell culture laboratory
  • A 250-kVp x-ray unit, a Cesium-137 irradiator, and two Cobalt-60 irradiators for cell and for total- and partial-body irradiations (Core Facilities of the Sloan Kettering Institute)

In addition, the laboratory has extensive computer hardware and software resources, as well as programming expertise. Specialized computer programs, such as AVS, IDL, MedX, and MatLab for general image display and analysis, SAAM for compartmental modeling, and MIRDOSE III for internal dosimetry are available. Application software is also developed in-house as needed and includes the state-of-the-art 3D internal radionuclide dosimetry package 3D-ID and the multimodality image manipulation and fusion package MIAU.