Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers

Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-...

Full description

Saved in:
Bibliographic Details
Published in:Journal of nuclear cardiology 2019-08, Vol.26 (4), p.1327-1344
Main Authors: Panwar, Rajiv, Bhattarai, Prashant, Patil, Vishwesh, Gada, Keyur, Majewski, Stan, Khaw, Ban An
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - adverse effects
ANTIBODIES
Antibodies, Bispecific
Cardiology
Cardiotoxicity - diagnostic imaging
Cardiotoxicity - etiology
Disease Models, Animal
DOXORUBICIN
Doxorubicin - adverse effects
Doxorubicin cardiotoxicity
Drug dosages
DTPA
gamma imaging
Imaging
Male
Medicine
Medicine & Public Health
MICE
Mice, Inbred BALB C
MYOSIN
Nuclear Medicine
Original Article
Pentetic Acid
polymer-drug conjugates
POLYMERS
pretargeting with bispecific antibody
RADIOACTIVITY
Radiology
RADIOLOGY AND NUCLEAR MEDICINE
SCINTILLATION COUNTING
Technetium
TECHNETIUM 99
Tomography, Emission-Computed, Single-Photon
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed. Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others. Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group. Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.
ISSN:1071-3581
1532-6551
1532-6551
DOI:10.1007/s12350-018-1190-2