james b. slater, rph, phd

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JAMES B. SLATER, RPH, PHD Director, UCSF Radiopharmaceutical Facility

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Page 1: JAMES B. SLATER, RPH, PHD

JAMES B. SLATER, RPH, PHD Director, UCSF Radiopharmaceutical Facility

Page 2: JAMES B. SLATER, RPH, PHD

¨  Purpose

¡  Describe cyclotron services ¡  Develop a communication pathway with

investigators ¨  Objectives

¡  Introduce the cyclotron staff ¡  Mission of the cyclotron laboratory ¡  Current and potential PET drugs available ¡  Process of ordering PET drugs ¡  FDA requirements for human use.

Page 3: JAMES B. SLATER, RPH, PHD

¨  Personnel ¡  James B. Slater, RPh, PhD

ú  Chemistry BS 1972 ú  Pharmacist RPh 1975 ú  Radiopharmacist MS 1977 ú  Pharmaceutical Chemistry (radiopharmaceutical) PhD 1982 ú  Director, Radiopharmacist/radiochemist UCSF 2006-present

¡  Allan Rosete, PharmD ú  Chemical Engineer BS 1991 ú  Pharmacist PharmD 2010 ú  Radiopharmacist UCSF 2010-present

¡  Salma Jivan BSc Diploma of Technology ú  BSc 1979 ú  Dipolma of Technology 1981 ú  Radiochemist UBC/TRIUMF PET Centre 1981-2012 ú  Radiochemist UCSF 2012-present

¡  Cyclotron engineers ú  William Mannone ú  Jeffrey Krug

Page 4: JAMES B. SLATER, RPH, PHD

¨  Official Name ¡  UCSF Radiopharmaceutical Facility

aka UCSF Cyclotron Laboratory

¨  Classification ¡  UCSF Radiology and Biomedical Imaging Core

services ¡  UCSF Shared Research Facility Level 2 ¡  FDA registered PET drug manufacturer

Page 5: JAMES B. SLATER, RPH, PHD

¨  Mission

¡  Manufacture PET drugs for routine clinical studies ¡  Manufacture PET Drugs for investigational clinical

and animal studies ¡  Provide PET drugs and isotopes for basic science

research ¡  Provide assistance in protocol design using

radiopharmaceuticals and pharmaceuticals

Page 6: JAMES B. SLATER, RPH, PHD

¨  Current PET drugs ¡  Routine clinical

ú  FDG ú  Ammonia ú  NaF

¡  Investigational ú  F18 FLT ú  F18 FMISO ú  F18 SFB ú  C11 Methionine ú  O15 water ú  I124 MIBG

¡  Other cyclotron projects ú  Zr-89 labeled antibody PD-1 ú  Ga-68 chelates (proposed)

Page 7: JAMES B. SLATER, RPH, PHD

PET DRUG MECHANISM

¨  N13 Ammonia

¨  O15 Water

¨  F18 SFB

¨  Cardiac perfusion

¨  Perfusion

¨  Protein labeling

Page 8: JAMES B. SLATER, RPH, PHD

PET DRUG MECHANISM

¨  F18 FDG

¨  F18 FLT

¨  F18 FMISO

¨  I124 MIBG

¨  C11 Methionine

¨  F18 NaF

¨  Glucose metabolism

¨  Cell division

¨  Hypoxia

¨  Neuroendocrine

¨  Amino acid tracer

¨  Osteogenic activity

Page 9: JAMES B. SLATER, RPH, PHD

PET DRUG MECHANISM

¨  F18 FES

¨  F18, C11 Choline

¨  F18, C11 Acetate

¨  F18 FMT*

¨  Estrogen receptors

¨  Metabolism

¨  Metabolism

¨  Amino acid tracer

Page 10: JAMES B. SLATER, RPH, PHD

PET DRUG MECHANISM

¨  F18 FDOPA*

¨  C11 Raclopride

¨  C11 DASB

¨  C11 MRB

¨  C11 Yohimbine

¨  C11 DTBZ

¨  dopaminergic pathway ¨  D2 receptors

¨  Serotonin transporter

¨  Norepinephrine trans NET

¨  Alpha adrenoceptors

¨  VMAT-2

Page 11: JAMES B. SLATER, RPH, PHD

PET DRUG MECHANISM

¨  C11 Sch23390 ¨  C11 PK11195

¨  C11 PMP ¨  C11 MDL100907 ¨  C11 PIB ¨  F18 FHBG

¨  D1 receptor antagonist ¨  Peripheral benzodiazepine

receptor ¨  Acetyl cholinergic

presynaptic receptors ¨  5-HT2A antagonist ¨  Beta-amyloid ¨  Reporter probe herpes

simplex

Page 12: JAMES B. SLATER, RPH, PHD

PRECURSOR PURPOSE PRECURSOR DEVELOPMENT

¨  Direct the isotope to a particular site

¨  Eliminate side reactions

¨  In house ¨  Outside GMP

manufacturers

Page 13: JAMES B. SLATER, RPH, PHD

¨  Current PET drug ¡  First time ordering a non-routine PET drug 1 month advanced

notice. ¡  Second time ordering the same non-routine PET drug 48 hour

advanced notice ¨  New PET drug

¡  First time ordering a new PET drug 3-4 months advanced notice ¡  Second time ordering the same non-routine new PET drug 48 hour

advanced notice. ¨   Information on PET Drugs Availability and Pricing

¡   http://www.radiology.ucsf.edu/research/core-services/probes ¡  Click on the 2013 DRUG PRODUCT CATALOG - PDF

¨  Pricing for assistance in proposal preparation is available ¨  It is critical to know about your requests as soon as

possible to provide the best service possible

Page 14: JAMES B. SLATER, RPH, PHD

¨  Critical information ¡  Labeled compound same as an endogenous

compound ¡  Previously used in humans

¨  Procedure for development ¡  Develop procedures and SOPs for manufacturing ¡  Develop procedures and SOPs for quality control ¡  Create batch record ¡  Three consecutive runs need to pass all QC

requirements ¡  Filing IND or RDRC

Page 15: JAMES B. SLATER, RPH, PHD

¨  Quality control requirements ¡  Appearance-visual inspection ¡  Sterility-filter membrane integrity test ¡  Radiochemical identity-HPLC or TLC ¡  Radiochemical purity-HPLC or TLC ¡  Radionuclidic identity-half life calculation ¡  Radionuclidic purity-MCA spectrum ¡  Chemical purity-GC (residual solvents) and/or

HPLC ¡  Bacterial endotoxins test- PTS ¡  Sterility testing-FTM and TSB media

Page 16: JAMES B. SLATER, RPH, PHD

¨  Contact information ¡  E-mail

ú  [email protected] ú  [email protected] ú  [email protected]

¡  Phone numbers ú  415-353-4435 ú  415-353-4476