PAC presentation Anca V2

1Challenge the future

Stability of polymersomes containing 111In using Perturbed Angular Correlation spectroscopy

Anca Tacu

Supervisor: Peter Bode


1. Introduction

2. Data Interpretation

3. Results & Discussion

4. Conclusion

5. Future Work


Cancer

Tumour tissueIncreased permeability of blood vessels

Dysfunctional lymphatic drainage

Accumulation nanocarriers


Polymersomes

Radionuclide 111InIonophore Tropolone

Chelator DTPA


Polymersomes


Chelator DTPA


Loading efficiencylpmoltC

In/5.0)( 0111

lpmoltCCd

/86.1)( 0111

Efficiency of loading dependent on:• age of stock solution • type of buffer


PACMeasures correlation between the directions of emission of 2 consecutive γ-rays

Directional probability of emission dependent on:•orientation of the nuclear spin axis •surrounding electrical field


Stop,θ

Clock,t1

2

θ

Start

Differentiate between different surrounding media of the radionuclide studied

PAC


PAC

180 9022

22 22 180 90

12

N NG

A Q N N

180 9022

22 22 180 90

12

N NG

A Q N N

22 0.5G

Highly perturbed 0 ≤ G22 ≤ 1 No perturbation


PAC

Parameters:• Relaxation time• The skn(η) coefficients• The precession frequencies: ωkn(η)

),cos()(3

0

tsetG knn

knt

kkk


Data interpretation

ERRONEOUS!

Standard deviation

ValueParameter


Results & Discussion3 sets of measurements:

• 111InCl3 crystalized and in solution at pH 2

• 111In-DTPA and 111In-Tropolone complexes

• 111In loaded polymersomes


Results & DiscussionSpecifications sample

Activity sample

Time since Calibration

Experimental Reference

Crystalized InCl3 300 kBq 10 d -0.15 0.14-0.02

Liquid 111InCl3 300 kBq 11 d 1.48 0.98Liquid 111InCl3 (liquid nitrogen)

0.08

22G

180 9022

22 22 180 90

12

N NGA Q N N

0 ≤ G22 ≤ 1A22 = -0.0870Q22 = 0.8066N180-N90<0

22G


Results & DiscussionSpecifications sample Activity

sampleTime since calibration

111In-DTPA in HEPES 130 kBq 17 d 0.31111In-DTPA in HEPES (liquid nitrogen) -0.57 111In-DTPA in PBS 0.57 111In-DTPA in PBS (liquid nitrogen) -1.93111In-Tropolone in HEPES 420 kBq 15 d 0.04 111In-Tropolone in PBS 0.23 111In-Tropolone in PBS (liquid nitrogen) -1.23

22G

Issue with the detectorOR

Correlation times of molecules too small to be detected by the PAC


Stability vs. Instability180 90

2222 22 180 90

12

N NGA Q N N

A22 = -0.0870Q22 = 0.8066

N180-N90<0

Assumption 180o detector stable: N180=90 000Case 1:

N90=60 000N90=100 000

Case 2:

22 0.67G 22 2.03G


Results & DiscussionSpecifications sample Activity

sampleTime since calibration

200 nm polymersomes in PBS

1st day 170 kBq 1 d 0.39 2nd day 130 kBq 2 d 0.26

200 nm polymersomes in HEPES

1st day 140 kBq 9 d 0.042nd day 110 kBq 10 d 0.17


2nd day 140 kBq 10 d 0.12


2nd day 170 kBq 10 d -0.05

22G

Size of polymersome seems not to have any influencePerturbation in HEPES polymersome seems to be higher than in PBS onesDoes the age of stock solution matter?


Conclusion• PAC has potential

• The system seems to have technical problems

• Winfit was not a reliable software

• No final conclusions could be drawn- more

measurements should be made


Future work1. Investigate:

• the influence of In3+

• the effect of Cd2+

• life-time of polymersomes upon systemic administration (in vivo & in vitro)

2. Was it just a problem with the detectors?

3. Purchase/ Implement a program for the data fitting


Thank you

PAC presentation Anca V2

Documents

Transcript of PAC presentation Anca V2