Cancer Research UK and Engineering and
Physical Sciences Research Council support to the Cancer Imaging Centre at
The Institute of Cancer Research (ICR) and the Royal Marsden Hospital NHS
Foundation Trust (RMH) in association with Medical Research Council and
Department of Health C1060/A10334, C1060/A16464

A Konik

AB Hwang

BF Hutton

C Hindorf

C Vanhove

C Wu

CH Chen

CJ Dean

CL Chen

CM Finucane

EJ Hoffman

F Sanchez

GD Ayers

I Kawrakow

JG Mannheim

JK Sosabowski

JK Willmann

JM Styles

JP Pouget

KF Eckerman

KJ Frisch

M Montelius

MA Bakir

MF Kircher

MS Cooper

P Workman

R Weissleder

S Boutaleb

SM Allan

SM Bentzen

SM Srinivas

T Kostou

T Mauxion

TJ Spinks

WJ Smellie

Y Seo

EJNMMI Research

PubMed

Springer - Publisher Connector

Pre-clinical quantitative imaging and mouse-specific dosimetry for In-labelled radiotracers

BACKGROUND: Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of 111In-labelled radiotracers. Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes. Six SK-OV-3-tumour bearing mice were injected with 111In-labelled HER2-targeting monoclonal antibodies (mAbs) (range 5.58-8.52 MBq). Sequential SPECT imaging up to 197 h post-injection was performed using the Albira SPECT/PET/CT pre-clinical scanner. Mice were culled for quantitative analysis of biodistribution studies. The tumour activity, mass and percentage of injected activity per gram of tissue (%IA/g) were calculated at the final scan time point and compared to the values determined from the biodistribution data. Delivered 111In-labelled mAbs tumour absorbed doses were calculated using mouse-specific convolution dosimetry, and absorbed doses for 90Y-labelled mAbs were extrapolated under the assumptions of equivalent injected activities, biological half-lives and uptake distributions as for 111In. RESULTS: For the sphere sizes investigated (volume 0.03-1.17 ml), the calibration factor varied by a factor of 3.7, whilst for the range of tumour masses in the mice (41-232 mg), the calibration factor changed by a factor of 2.5. Comparisons between the mice imaging and the biodistribution results showed a statistically significant correlation for the tumour activity (r = 0.999, P < 0.0001) and the tumour mass calculations (r = 0.977, P = 0.0008), whilst no correlation was found for the %IA/g (r = 0.521, P = 0.29). Median tumour-absorbed doses per injected activity of 52 cGy/MBq (range 36-69 cGy/MBq) and 649 cGy/MBq (range 441-950 cGy/MBq) were delivered by 111In-labelled mAbs and extrapolated for 90Y-labelled mAbs, respectively. CONCLUSIONS: This study demonstrates the need for multidisciplinary efforts to standardise imaging and dosimetry protocols in pre-clinical imaging. Accurate image quantification can improve the calculation of the activity, %IA/g and absorbed dose. Diagnostic imaging could be used to estimate the injected activities required for therapeutic studies, potentially reducing the number of animals used

Denis-Bacelar, AM

Cronin, SE

Da Pieve, C

Paul, RL

Eccles, SA

Spinks, TJ

Box, C

Hall, A

Sosabowski, JK

Kramer-Marek, G

Flux, GD

Institute of Cancer Research Repository

Pre-clinical quantitative imaging and mouse-specific dosimetry for 111In-labelled radiotracers.

Ana M. Denis-Bacelar

Sarah E. Cronin

Chiara Da Pieve

Rowena L. Paul

Sue A. Eccles

Terence J. Spinks

Carol Box

Adrian Hall

Jane K. Sosabowski

Gabriela Kramer-Marek

Glenn D. Flux

Crossref

Pre-clinical quantitative imaging and mouse-specific dosimetry for 111In-labelled radiotracers

Queen Mary Research Online