A preclinical model for predicting drug response in soft-tissue sarcoma with targeted AAVP molecular imaging.
Human sarcomas are rare but diverse malignant tumors derived from mesenchymal tissue. Clinical response to therapy is currently determined by the modified World Health Organization (WHO) criteria or the Response Evaluation Criteria in Solid Tumors (RECIST), but these standards correlate poorly with sarcoma patient outcome. We introduced ligand-directed particles with elements of AAV and phage (AAVP) to enable integration of tumor targeting to molecular imaging. We report drug-response monitoring and prediction in a nude rat model of human sarcoma by AAVP imaging. As a proof-of-concept, we imaged Herpes simplex thymidine kinase in a clinic-ready setting with PET to show that one can a priori predict tumor response to a systemic cytotoxic. Given the target expression in patient-derived sarcomas, this platform may be translated in clinical applications. Sarcoma-specific ligands and promoters may ultimately lead to an imaging transcriptome.
Hajitou
Amin
A
The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Lev
Dina C
DC
Hannay
Jonathan A F
JA
Korchin
Borys
B
Staquicini
Fernanda I
FI
Soghomonyan
Suren
S
Alauddin
Mian M
MM
Benjamin
Robert S
RS
Pollock
Raphael E
RE
Gelovani
Juri G
JG
Pasqualini
Renata
R
Arap
Wadih
W
D000818:Animals; D001435:Bacteriophages / Q000235:genetics*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D008024:Ligands; D051379:Mice; D051381:Rats; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D019076:Transgenes / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D008024:Ligands