EMAIL THIS PAGE TO A FRIEND

EJNMMI research

Immuno-PET of epithelial ovarian cancer: harnessing the potential of CA125 for non-invasive imaging.


PMID 26116121

Abstract

Epithelial ovarian cancer (EOC) is characterized by the overexpression of cancer antigen 125 (CA125), a mucinous glycoprotein that serves as a tumor biomarker. Early diagnosis of EOC is plagued by its asymptomatic nature of progression and the limitations of currently used immunoassay techniques that detect CA125 as a shed antigen in serum samples. Presently, there is no technique available for the in vivo evaluation of CA125 expression in malignant tissues. Moreover, there could be an unexplored pathophysiological time window for the detection of CA125 in EOC, during which it is expressed on tumor cells prior to being shed into the bloodstream. A method for the in vivo evaluation of CA125 expression on ovarian neoplasms earlier along disease progression and/or recurrence can potentially contribute to better disease management. To this end, the present work utilizes an anti-CA125 monoclonal antibody (MAb) and a single-chain variable fragment (scFv) labeled with the positron-emitting radionuclide (64)Cu for preclinical molecular imaging of CA125 expression in vivo. Anti-CA125 MAb and scFv were prepared and functionally characterized for target binding prior to being tested as radiotracers in a preclinical setting. Immunoblotting, immunofluorescence, and flow cytometry revealed specific binding of CA125-targeting vectors to NIH:OVCAR-3 cells and no binding to antigen-negative SKOV3 cells. (64)Cu-labeled anti-CA125 MAb and scFv were obtained in specific activities of 296 and 122 MBq/mg, respectively. Both radioimmunoconjugate vectors demonstrated highly selective binding to NIH:OVCAR-3 cells and virtually no binding to SKOV3 cells. In vivo radiopharmacological evaluation using xenograft mouse models injected with (64)Cu-labeled anti-CA125 MAb provided a standardized uptake value (SUV) of 5.76 (29.70 %ID/g) in OVCAR3 tumors 24 h post-injection (p.i.) versus 1.80 (5.91 %ID/g) in SKOV3 tumors. (64)Cu-labeled anti-CA125 scFv provided an SUV of 0.64 (3.21 %ID/g) in OVCAR3 tumors 24 h p.i. versus 0.25 (1.49 %ID/g) in SKOV3 tumors. Results from small-animal PET imaging were confirmed by ex vivo autoradiography and immunohistochemistry. Radiolabeling of anti-CA125 MAb and scFv with (64)Cu did not compromise their immunoreactivity. Both radioimmunoconjugates presented specific tumor uptake and expected biological clearance profiles. This renders them as potential immuno-PET probes for targeted in vivo molecular imaging of CA125 in EOC.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

C2978
CelLytic M, Cell Lysis Reagent, Suitable for Mammalian cell lysis and protein solubilization.
411000
Ethanolamine, purified by redistillation, ≥99.5%
C2H7NO
398136
Ethanolamine, ACS reagent, ≥99.0%
C2H7NO
ARK2169
Ethanolamine, PharmaGrade, USP/NF, Manufactured under appropriate GMP controls for Pharma or biopharmaceutical production
C2H7NO
E9508
Ethanolamine, ≥98%
C2H7NO
E0135
Ethanolamine, liquid, BioReagent, suitable for cell culture, ≥98%
C2H7NO
15014
Ethanolamine, ≥99%
C2H7NO
P7700 Protein G–Agarose, lyophilized powder, Contains lactose stabilizers that must be removed prior to use.
S2889
Sodium acetate, anhydrous, for molecular biology, ≥99%
C2H3NaO2
S5636
Sodium acetate, powder, BioReagent, for electrophoresis, suitable for cell culture, suitable for insect cell culture, ≥99%
C2H3NaO2
S1429
Sodium acetate, meets USP testing specifications, anhydrous
C2H3NaO2
229873
Sodium acetate, 99.995% trace metals basis
C2H3NaO2
S7545
Sodium acetate, BioXtra, ≥99.0%
C2H3NaO2
71183
Sodium acetate, anhydrous, BioUltra, for luminescence, for molecular biology, ≥99.0% (NT)
C2H3NaO2
W302406
Sodium Acetate Anhydrous, >99%, FCC, FG
C2H3NaO2
71196
Sodium acetate solution, BioUltra, for molecular biology, ~3 M in H2O
C2H3NaO2
339113
Tantalum(V) ethoxide, 99.98% trace metals basis
C10H25O5Ta
760404
Tantalum(V) ethoxide, packaged for use in deposition systems
C10H25O5Ta