PAC presentation Anca V2

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Stability of polymersomes containing 111In using Perturbed Angular Correlation spectroscopy

Anca Tacu

Supervisor: Peter Bode

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1. Introduction

2. Data Interpretation

3. Results & Discussion

4. Conclusion

5. Future Work

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Cancer

Tumour tissueIncreased permeability of blood vessels

Dysfunctional lymphatic drainage

Accumulation nanocarriers

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Polymersomes

Radionuclide 111InIonophore Tropolone

Chelator DTPA

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Polymersomes

Radionuclide 111InIonophore Tropolone

Chelator DTPA

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Polymersomes

Radionuclide 111InIonophore Tropolone

Chelator DTPA

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Loading efficiencylpmoltC

In/5.0)( 0111

lpmoltCCd

/86.1)( 0111

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

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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

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Stop,θ

Clock,t1

2

θ

Start

Differentiate between different surrounding media of the radionuclide studied

PAC

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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

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PAC

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

),cos()(3

0

tsetG knn

knt

kkk

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Data interpretation

ERRONEOUS!

Standard deviation

ValueParameter

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Results & Discussion3 sets of measurements:

• 111InCl3 crystalized and in solution at pH 2

• 111In-DTPA and 111In-Tropolone complexes

• 111In loaded polymersomes

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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

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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

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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

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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

400 nm polymersomes in HEPES

2nd day 140 kBq 10 d 0.12

800 nm polymersomes in HEPES

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?

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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

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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

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Thank you