Week 7
Nuclear characteristics of F18
- low positron energy with high abundance
- synthetically desirable half-life (109 min)
- readily available and can be made w/ high SA (only 18O method)
what can FDG tell us what are its limitations of FDG
Presence of tumours, metastases, treatment progression, staging, recurrence
Limitations:
- false positives (inflammation)
- false negatives (small metastases/bone)
what is parkinsons? why use DOPA and not DOPAMINE
progressive/degen disease, lower dopamine production of neurons in substantial nigra, resulting in poor gait/memory
y? BBB
how to prepare a 99mTc-MDP using a kit? why can't we characterize this diagnostic?
1. mix in 99m Tc
2. swirl
3. let it sit for 10 min
4. confirm purity
5. write dates/times/names
6. inject with shielded needle
we can't because 99mTc does not exist in 'cold' versions so we can't characterize the compound
4 ways to measure iTLC
1. cut in half (only for well established)
2. cut into cm chunks
3. machine imaging w inert gas, cps
4. phosphor imaging
Iodine radiochemistry (2 routes, oxidizing agents)
indirect (via BH) vs direct (via tyr residues)
Oxidants: chlormaine T, iodogen -> lead to I+ formation
why are we progressing away from C-F chemistry? what is an example of non C-F chemistry?
- harsh reaction conditions, multisitep, lengthy
example: SiFA, AlF
why is production of [18F]F2 from Neon low in SA? problems with F2?
gets stuck to target must be flushed with cold fluorine (carrier-added) resulting in lower specific activity
F2 problems: extremely reactive, nonchemoselective, harsh conditions, low RCC
why use MPI? what are the anatomical planes? what is roll off effects?
bonus: what imaging agent suffers least roll-off effects
- myocardial perfusion imaging: diagnose areas of infarct/ischemia, pre op, cardiotoxicity, prognosis post blood clot
- SA (circle ), VLA (backwards C), HLA (upside down U)
- roll off: higher BF lowers tracer uptake
- bonus: 18F-flurpiridaz
what conditions can we not use beta therapy? why?
hypoxic, as primary MOA is via generation of free radicals to cause DNA strand breaks
How does PET work and how can we convert signal to visible light?
positron decay results in annihilation of positron with electron in environment.
leads to ejection of two 511 keV rays 180deg from each other.
Can be picked up by detector blocks which are crystals (BGO, LYSO) that emit visible light upon detection/relaxation to allow for imaging.
explain pre-targeting experiment
what is advantageous about this?
1. inject targeting vector
2. let it circulate
3. inject radio tracer + prosthetic group
4. click + image
advantage: can use shorter lived isotope (lower exposure)
production route of 11C
wet/dry method to convert to methyl iodide
14N(p,a)11C
- bombard with O2 -> CO2
- bombard with H2 -> CH4
Wet method: (CO2) LiALH4 reduction then iodination
Dry method: (CH4) I2 high temp, continuous extraction
characteristics of a good MPI tracer
- high heart uptake, slow clearance
- fast blood clearnace, minimal uptake in neighbouring organs
- quantifiable signal, high sensitivity to changes in blood flow
- ideal t1/2 (either long, or short for serial administration)
- readily available/easy to synthesize
3 types of theranostics? example case study?
- radiohybrid-> 2 spots for each nuclide
- elementally matched -> same nuclide different radioisotope
- comparable elements -> 68Ga + 177Lu
Ex: NETSPOT/lutathera
RCC vs DC/NDC-RCY vs RCP vs activity yield
(what, how to quantify)
RCC: how much was labelled with something, iTLC
RCY: how much activity is left after reaction (DC/NDC), dose calibrator
RCP: how much of activity is pure tracer, HPLC (co-injection)
Activity yield: activity of how much after purification
Hamacher synthesis of FDG vs F2 electrophilic synthesis
Hamacher: all hydroxyls PG with acetate, C2 has trifoliate that F w/ kryptofix can react with
Electrophilic: double bond C1-C2 18/19F adds to both sides, hydrolysis of C1*
*can get FDM/FDG which is axial/equitorial respectively @C2
what is PiB a derivative of? what biomarker does it target? synthesis? clinical use?
- thioflavin
- amyloid plaques
- methylate primary amine, deprotect phenol ring
- no clinical use as too short lived, attempt w/ 18F derivatives
make 99mTc from 99Mo, how to reduce to +5 charge?
what is useful about generators?
- Mo generator where Mo is -2 and sticks to alumina sorbent while Tc-1 is eluted off with sterile saline. Milk every 24 hours (4 half lives)
- react with SnCl2 to reduce from +7 to +5
can be portable (good esp for Canada), less shielding due to lower energy gamma
why consider alphas? give an example of one talked in class (benefits, difficulties, therapy)
- have higher LET, less travel distances (good for small metastases). double strand breaks
- 225Ac -> emits 4 alphas! but can only obtain from generator every 4-6 weeks from 229Th decay
- use for PSMA for prostate cancer treatment (good results!)
Process of extraction of [18F]F- from 18O Target water
1. seal up O-18 water, bombard for <4h
2. transfer target water into FH
3. trap on anion column
4. elute with kryptofix (make more Nu/soluble)
5. dry down x3
6. label!
4 strategies for aromatic F- reactions
1. Pd -> air sensitive, too hard for radio pharmacy
2. Ni -> no oxidation step req, slightly more simple
3. Iodinium salts: labelled preferentially on most electron deficient ring
4. Iodinium ylide: only labeled on one ring, specific!
captive solvent approach 11C-acetate, what is use?
1. add CO2 gas to vessel with Grignard already there
2. flush w/ DI water
3. cation exchange 2x
4. trap on anion exchange
5. elute with NaI
Use: myocardial oxidative metabolism, tumour imaging in higher glucose uptake areas (around liver, prostate, bladder)
Issues with Rb and Tl for MPI
- Rb: very short lived (admin directly into patients), interference of gamma rays, high doses, high roll off
- Tl: longer half life, will have uptake gradually even in ischemic areas
Lu production routes, macrocylic effect, SPECT ability... what can we use instead?
176Lu(n,y)177Lu (CA)
176Yb(n,y)177Yb 177Lu (NCA)
macrocyclic effect: favourable to interact with cyclic compounds then acyclic
SPECT: poor imaging agent, low energy gamma, need lots of activity to make out resolution can use 68Ga for PET (+3 as well, same chelator) obtain similar to Molly cow