Radiochemistry Solutions

Leadership in radiopharmaceuticals production Total Solution Provider Eclipse: Upgradeable cyclotrons Explora: Full line of radiochemistry modules Start up and continued support for current and future growth

A broad range radiochemistry offering Explora FDG4 Quality FDG production Explora CN Cyanide synthesis Explora GPU Gas processing Explora AC Produces acetate Explora H2O 15O water module Explora FDG4 Explora CN Explora AC Explora H2O

Explora FDG4 specifications 45 minute synthesis 75% decay corrected yield 4 runs without intervention Novel recipe building software Remote diagnostic capability Automatic self-cleaning Rich user feedback (radiation, temperature, pressure sensors) Low cost of operation Minimal custom parts (uses conventional disposable glassware)

Explora FDG4 – Multirun synthesis module Convenient - Smart - Reliable 4 runs without intervention Remote diagnostic capability Automatic self-cleaning Rich user feedback (radiation, temperature, pressure sensors) Low cost of operation Run number Synthesis yield Total FDG 1 81% 6760 mCi 2 77% 5520 mCi 3 78% 6440 mCi 4 69% 5070 mCi 4 runs 76% average 23790 mCi total Daily Usage

Explora convenient 4 runs without intervention Set up once, run all day Kits are available for streamlined setup Reagents are inverted on disposable spikes No measurement of reagents – All calculations are performed automatically via software

Explora smart Everything you need to know to optimize performance Feedback of temperature, pressure, radiation All data recorded for playback can see performance in trapping, labeling, hydrolysis Synthesis data synopsis guides performance improvement Remote operation and test capability Software speaks like, and understands, chemists

Explora reliable 4 runs/day with > 20 Ci production yield of FDG Has been utilized to make over 8 Ci of FDG in a single run Has made over 150,000 batches of FDG in PETNET commercial pharmacies 40% more likely than other commercial systems to provide yields over 75% > 99% uptime Raw data from PETNET network records October 2004 – Mar 2008

Explora summary The superior choice Reliable Powerful Convenient Smart Inexpensive Flexible Safe The superior choice

Explora AC – 11C Acetate module Produces 11C acetate and other Grignard tracers. Fully automated with high yields Decay corrected yields >70%

Explora CN – 11C Cyanide module For producing 11C amino acid precursors Produces high yields of 11C HCN or 11C CH4 Decay corrected yields >55%

Explora H2O – 15O Water module Provides inexpensive unit doses of 15O labeled water Disposable cartridge Self shielded Simplified siting Can be placed next to scanner bed

Explora GPU – Gas processing unit For the production of 15O and 11C gases 15O2 C15O, C15O2 11CO2 11CO Flow chemistry No minicells needed Placed inside the cyclotron shields

Newly introduced chemistry modules Explora GN For general nucleophilic reactions including FLT Explora GPC Methyl iodide synthesis Explora CH3 Methylation module AND Two new purification modules Explora FM Explora LC Explora GN Explora GPC Explora CH3 Explora FM Explora LC

Explora GN – Built on the reliability and efficiency of FDG4 Compatible with most nucleophilic solvents Capable of delivering small reagent volumes with virtually no loss – cost benefit when using expensive precursors Option to synthesize FDG New software supports pressurized reaction steps Integrates with semi-prep HPLC modules (Explora LC) and formulation module (Explora FM)

Explora GN application flexibility Synthesis and purification options Seamless integration to purification modules Explora GN Explora FM Explora LC FDG F-MISO NaF FLT

Explora GPC – Versatile solution for methyl iodide synthesis Key Features Flexible and completely automated module for gas phase synthesis of 11C methyl iodide Consistently generates high specific activity methylating agents Capable of accepting 11C CO2 or 11C methane gas Provides continual feedback to user via comprehensive monitoring via radiation detectors, iodine vapor density tracking, mass flow controller monitoring and feedback, pressure transducer trace and multiple temperature readouts Concentrates and traps 11C methyl iodide and releases only when ready for subsequent steps Capable of 15 runs between refilling / reconditioning of 11C methyl iodide

Methyl iodide synthesis – the “traditional” method Unintended and undesirable accumulation leading to component failure Intended accumulation leading to frequent servicing Intended depletion leading to frequent servicing Methyl iodide trap Unintended and undesirable accumulation leading to frequent servicing Time for service!

“Improved” methyl iodide synthesis – The Siemens method Methane in Methyl Iodide out Key advantages - Intervention into the device is minimized, thereby providing High uptime Low personnel dose Very high specific activity

Explora CH3 - Methylation module Key Features Uses solvent-based chemistry for production of 11C methylated compounds Can be used in combination with Explora GPC Can accept various 11C methylating intermediates in gas phase from other sources

Explora FM – Formulation module Key Features Performs solid phase extraction (SPE) purification for final product formulation Capable of being setup for production of 18F NaF Flexible recipe builder software allows end user to design customer purification schemes

Explora LC – Semi-prep HPLC purification module Key Features Semi-prep or analytical radio-HPLC for purification of crude radiopharmaceuticals Novel loop loading method without using problematic bubble detectors Back-to-back run capability Automated column switching Automated column cleaning – no manual solvent switching Automated fraction collection via either UV signal or radiation detection Control software complies to the guidelines specified in the 21 CFR Part 11 for the storage and protection of electronic archived data and electronic signatures. Product includes HPLC pump, UV and radiation detector, solvent switching valve, fraction collection valve and loop loading valve with 2 loop positions