NON-INVASIVE CHARACTERIZATION OF PROSTATE CANCER WITH HYPERPOLARIZED 13C N-ACETYL ASPARTYLGLUTAMATE
Publication Date: 2015-Apr-15
The IP.com Prior Art Database
The disclosed invention provides a technique to perform targeted imaging of prostate cancer using magnetic resonance (MR) and targeted contrast base on prostate specific membrane antigen (PSMA) expression. The technique uses pre-polarized carbon-13 (13C) labeled substrate of an enzyme to perform targeted imaging of prostate cancer. Further, activity is realized when the pre-polarized substrate is metabolized by the enzyme and provides a change in chemical shift observed in the MR spectrum.
The present invention relates generally to imaging agents targeting prostate specific membrane antigen (PSMA) and more particularly to a technique to provide non-invasive characterization of prostate cancer.
Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA) is a transmembrane folate hydrolase encoded by the folate hydrolase1 (FOLH1) gene. GCPII is expressed in tissues of central nervous system, kidneys and prostate. The enzyme catalyzes hydrolysis of N-acetylaspartylglutamate (NAAG) to glutamate and N-acetylaspartate and also cleaves terminal glutamate from gamma-linked folate polyglutamate. PSMA is used as a target for imaging and therapeutic agents for prostate cancer due to correlation of elevated expression of PSMA with tumor grade, pathological stage and recurrence of the disease.
Elevated PSMA expression in prostate cancer includes primary prostate cells. Prostate enzyme has activity in both membrane and cytosolic fractions termed PSMA and PSMA', respectively. Using NAAG hydrolytic radioenzymatic assay, enzymatic activity of PSMA and PSMA' is quantitated in normal, benign prostatic hyperplasia (BPH), and prostate cancer (PC) tissues from radical prostatectomies. PSMA enzyme activity is evaluated in each tissue type and expressed per milligram protein and epithelial cell content. It is observed that prostate carcinogenesis is associated with an elevation in PSMA and PSMA' enzyme activity.
Further, the PSMA is linked to recurrence of prostate cancer disease and poorer survival.
Conventional techniques utilizing PSMA as target for prostate cancer imaging rely on radio-labeled peptides that bind specific to PSMA. For example, in one of the approaches food and drug association (FDA) approved Indium 111 capromab pendetide is utilized whereas in another approach small molecular weight variants are utilized. Indium 111 capromab pendetide is an FDA approved radiolabeled antibody of PSMA for use as a single-photon emission computed tomography (SPECT) imaging agent in prostate cancer patients. However, Indium 111 capromab pendetide exam suffers from low specificity, and issues inherent of SPECT technique and large molecular weight agents. Also, neither of the approaches utilizes enzyme activity of protein that is known to increase in expression and also its activity.
It would be desirable to have an efficient technique to provide non-invasive characterization of prostate cancer.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1 depicts possible hydrolysis of NAAG by PSMA.
The disclosed invention provides a technique to perform targeted imaging of prostate cancer using magnetic resonance (MR) and targeted contrast base on prostate specific membrane antigen (PSMA) expression. The technique uses pre-polarized carbon-13 (13C) labeled substrate of an enzyme to perform targeted imaging of p...