“Graduate Studies in Radiochemistry at University of Missouri”. Susan Z. Lever Biomedical Program Director, MURR Associate Professor of Chemistry. Highest concentration of “radiochemistry” research scientists on any campus Breadth and diversity of research topics
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Susan Z. Lever
Biomedical Program Director, MURR
Associate Professor of Chemistry
Highest concentration of “radiochemistry” research scientists on any campus
Breadth and diversity of research topics
Vet School, Med School on the same campus
Interdisciplinary research possibilities
Law School, Business School on campus
Student population has a range of interests
Journalism School and School of Education
Cross-discipline possibilitiesThings to know about MU #1:
Highest flux research reactor of any US campus scientists on any campus
High field nmrs, with an 800 MHz on order
Cyclotron to be installed in 2007
Small animal imaging capabilities include SPECT, PET, MRI and CTThings to know about MU #2:
Long history of radiopharmaceutical development scientists on any campus
Established program in archeometry
World-renowned location for contribution of trace metal analyses to biomedical problems
Active grant funding and current projects in the above areasThings to know about MU #3:
Blood Flow during Meditation scientists on any campus
Andrew Newberg, University of Pennsylvania
http://www.andrewnewberg.com/ accessed 6/21/05
Design, synthesis and evaluation of novel biological targets for diagnosis and therapy
Bifunctional Chelate Approach
Thiolactone containing molecule was designed to permit one-step coupling with amine functionalities, and concomitant completion of the tetradentate core required for complexation.
Presence of the N-Methyl group yields charged complexes upon reaction with technetium.Bifunctional Chelate Approach for LabelingPeptides, Proteins and Antibodies with Tc
Approaches to radiolabeling reaction with technetium.
diprenorphine with radioiodine
J. L. Musachio and J. R. Lever, Tetrahedron Lett., 30, 3613-3616 (1989)
C6-O-iodoallyl-diprenorphine for reaction with technetium.in vivo studies of opioid receptors
Lever et al., Synapse 29: 172-182, 1998.
70 - 80% Radiochemical Yield
1200 - 1700 mCi /mol
58 - 84% Radiochemical Yield
> 2400 mCi /mol
2 Hours Total Time
MeOH / HOAc (95:5)
Chloramine-T, 2 min.
2. HPLC / Solid Phase
3. Formulation / QC
(5% EtOH /saline)
Saline Control Naltrexone Block
I reaction with technetium.
ISA4503, FESA4503 and Initial Analogs
E - iodoallyl
SA4503; R = 11CH3
FESA4503; R = 18FCH2CH2-
Z - iodoallyl
Elsinga et al., Synapse 43:259-267, 2002.
Ishiwata et al., Nucl. Med. Biol. 30:273-284, 2003.
24.50 ± 1.61c
15.10 ± 1.03c
22.0 ± 2.78c
20.3 ± 1.29c
Radiochemical Yields with 125I:
(57-58.5%) with high
Biodistribution of reaction with technetium.125I-Iodoallyl Analogs of SA4503 in normal mice:
Control and Blocked
Question: reaction with technetium.So, is there a chemical way to:
1) Decrease Lipophilicity and Retain Affinity?
New Iodoallyl analogs: reaction with technetium.
Biodistribution of “New and Improved” reaction with technetium.E125I-Iodoallyl Analog in normal mice:
In vivo reaction with technetium. performance of “New and Improved”
Trans IA-Sigma Ligand
Test drugs i.v. at 2.5 mol / kg. Values are means ± SD; n = 4.
Radiopharmaceutical Chemistry reaction with technetium.
also deals with Radiotherapy
Highest neutron flux of any U.S. university reactor reaction with technetium.
High reliability -- operates 105% of schedule [91% of clock time]
Traditionally access samples once/week
Currently access samples several times each weekFeatures of MURR
The Blue Glow reaction with technetium.
Lanthanides [all M reaction with technetium.3+]
Pm-149, Sm-153, Ho-166, Dy-166, Lu-177
Rh-105, Pd-109, Re-186, Ir-192, Au-198
Main Group Elements
P-32, P-33, Se-75Selected IsotopesCurrently Supplied by MURR
Isotope reaction with technetium.
b - (MeV)
Nuclear Properties of Various M3+ Radionuclides
PO reaction with technetium.
Development began in early 1980’s at MU in collaboration with the Dow Chemical Company [phosphonate ligands]
Successful in palliative treatment of bone cancer in canine patients, with added bonus of ~ 15% cure rate [MU College of Veterinary Medicine program of Comparative Oncology]
Clinical trials began in late 1980’s, with doses supplied by MURR for Phase I studies
~ 80% efficacy, with ~ 25% obtaining full pain remission
Approved in U.S. for pain palliation of metastatic bone cancer in March, 1997Story of QuadraMetTM
Effective treatment with minimal toxicity
Outpatient procedureYttrium-90 Microspheres
Yttrium is an integral part of the glass matrix
Delbert Day (University of Missouri - Rolla) and Gary Ehrhardt (University of Missouri - Columbia) U.S. Patent 4,789,501 December 6, 1988Yttrium-90 Microspheres
Y-89 microspheres are irradiated in the MU-Research Reactor (MURR), resulting in the conversion of the non-radioactive yttrium to Y-90, a powerful b- emitter (64.2 hr half-life, average distance in tissue: 2.5 mm)Preparation of Active Microspheres
In a recent study (Dancy et al., J. Nucl. Med. 41: 1673-1681, 2000), patients with hepatocellular carcinoma (HCC) were treated with 100 Gy
Outcome: 79% patients decreased or had stable disease for a median of 10.3 months vs. 1 - 4 months for untreated patientsYttrium-90 Microspheres
March, 2000: MDS Nordion (Kanata, Ont. Canada) was granted a Humanitarian Device Exemption by the U.S. Food and Drug Administration as an alternative to chemotherapy in inoperable casesYttrium-90 Microspheres become TheraSphere®
Five year grant award Humanitarian Device Exemption by the U.S. Food and Drug Administration as an alternative to chemotherapy in inoperable cases from the National Cancer Institute of the National Institutes of Health, 8/01/03 - 7/31/08
Complements on-going interdisciplinary research at MU focused on imaging and therapeutic applications of radioisotopes
Includes a career development component, supporting undergraduate research activities.Centerfor Single Photon-EmittingCancer Imaging Agents
Radiochemistry Program Humanitarian Device Exemption by the U.S. Food and Drug Administration as an alternative to chemotherapy in inoperable cases
Jurisson Group Research Humanitarian Device Exemption by the U.S. Food and Drug Administration as an alternative to chemotherapy in inoperable cases
Probes new coordination environments of actinides that bridge non-aqueous complexes with traditional systems found under environmental conditions.
J. David Robertson Humanitarian Device Exemption by the U.S. Food and Drug Administration as an alternative to chemotherapy in inoperable cases
Using the unique properties of the nucleus to study chemical processes/problems which, frequently, cannot be examined by other means.
Investigating the source and impact of fine airborne particulate
Elemental imbalances in the formation of Alzheimer’s disease
“Aging” the plaques and tangles in Alzheimer’s disease
Using red ochre for provenance studies
Evaluating children’s chronic exposure to As and Cr from Cu/Cr/As treated wood structures.
Population-Based Studies: institutions or museums in 46 statesCancer incidence or mortality is inversely proportional to regional indicators of status.
Case-Control Studies:In some case-control studies, selenium status, measured in a prospectively-collected biologic monitor, is lower in cancer cases compared to matched controls.
Intervention Trials:Cancer incidence and mortality risks are lower among participants taking a supranutritional selenium supplement compared to control subjects in double-blind, placebo-controlled trials.Epidemiological studies have associatedlow selenium intake with increased cancer risk
http://www.smartdraw.com/ institutions or museums in 46 states
Active Graduate Student Organization institutions or museums in 46 states
Geographically south of the glaciated till plain, so rolling hills heading to the Ozarks
Numerous caves for spelunking and rivers for floating
In between Kansas City and St. LouisThings to know about MU #4: