1. DB00089
Capromab
CATEGORY
Indicators and Reagents and Diagnostic Agents

2. DESCRIPTION
Capromab is a Murine IgG1 monoclonal 7E11-C5.3 antibody that recognizes prostate specific membrane antigen (PSMA - also known as glutamate carboxypeptidase 2) from prostate cancer cells and normal prostate tissue. It is linked to pendetide, a derivative of DTPA. Pendetide acts as a chelating agent for the radionuclide indium-111. Capromab is used to image the extent of prostate cancer.
INDICATION
For diagnosis of prostate cancer and detection of intra-pelvic metastases.
PHARMACODYNAMICS
Binds to the prostate-specific membrane antigen, which is a cell surface protein generally overexpressed in prostate tissues and prostate cancers. The radioactive Indium 111, which is covalently attached to the antibody, allows radio-diagnostic detection of PSMA expressing cells and tumors.

3. TARGET
Glutamate carboxypeptidase 2
MECHANISM OF ACTION
Binds selectively to cell-surface prostate-specific membrane antigen (PSMA) expressed on prostate tissues and tumors.
METABOLISM
Most likely removed by opsonization via the reticuloendothelial system or by human antimurine antibody production

4. ROUTE OF ELIMINATION
Approximately 10% of the administered radioisotope dose is excreted in the urine during the 72 hours following intravenous infusion.
VOLUME OF DISTRIBUTION 4 ± 2.1 L
CLEARANCE 42 +/- 22 mL/hr
DRUG INTERACTIONS
Buserelin:
Avoid combination because luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide.

5. Prostascint: Indium (111In) capromab pendetide
IV Infusion
Prostatic carcinoma, intra-pelvic metastases (diagnosis) and Prostatic carcinoma, occult, recurrence (diagnosis)—Indium In 111 capromab pendetide is indicated for use in immunoscintigraphy in patients with biopsy-proven prostate carcinoma who are at high risk for pelvic lymph node metastases. Indium In 111 capromab pendetide is also indicated in patients who have undergone a prostatectomy, and have rising prostate-specific antigen (PSA) values and equivocal or no evidence of metastatic disease on standard metastatic evaluation, but in whom there is a high clinical suspicion of occult metastatic disease.
—In phase 3 clinical trials, high-risk patients were defined as having one of the following: PSA ³ 10 times the upper limit of normal and Gleason score ³ 7; prostatic acid phosphatase above the upper limit of normal; equivocal evidence of lymph node metastases on computed tomography (CT) or ultrasound and PSA ³ 8 times the upper limit of normal; Gleason score ³ 8; clinical stage C and Gleason score

6. Capromab (MAb 7E11-C5.3), a murine monoclonal antibody of the immunoglobulin subclass IgG 1K, localizes or binds specifically to a prostate-specific membrane glycoprotein (PSMA) that is only expressed by prostatic epithelial cells (benign and malignant) {01}. The monoclonal antibody 7E11-C5.3 is site-specifically labeled with indium In 111 chloride using the linker-chelator, glycyl-tyrosyl-(N,epsilon-diethylenetriaminepentaacetic acid)-lysine hydrochloride or GYK-DTPA-HCl {01}. The resultant radiolabeled monoclonal antibody conjugate, 111In capromab pendetide (CYT-356), retains the immunoreactivity of the unconjugated monoclonal antibody. Following intravenous administration, the indium In 111–labeled capromab pendetide travels through the blood stream until it encounters tumors bearing the specific antigen. The distribution of radioactivity is recorded by imaging

7. Dosage: For detection of the extent and localization of prostatic carcinoma—Intravenous infusion, 0.5 mg of capromab pendetide radiolabeled with 185 megabecquerels (5 millicuries) of indium In 111 chloride, administered as a single dose over a period of five minutes
Clearance: Renal (10% of the administered activity excreted within 72 hours)
Half-life: 67 ± 11 h
Drug interaction: Digoxin (Lanoxin®). Consult doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products
Adverse reaction: allergy to drug components

8. References
Smith-Jones PM, Vallabahajosula S, Goldsmith SJ, Navarro V, Hunter CJ, Bastidas D, Bander NH: In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen. Cancer Res Sep 15;60(18):
Sodee DB, Nelson AD, Faulhaber PF, Maclennan GT, Resnick MI, Bakale G: Update on fused capromab pendetide imaging of prostate cancer. Clin Prostate Cancer Mar;3(4):230-8.
Gregorakis AK, Holmes EH, Murphy GP: Prostate-specific membrane antigen: current and future utility. Semin Urol Oncol Feb;16(1):2-12.
Sodee DB, Ellis RJ, Samuels MA, Spirnak JP, Poole WF, Riester C, Martanovic DM, Stonecipher R, Bellon EM: Prostate cancer and prostate bed SPECT imaging with ProstaScint: semiquantitative correlation with prostatic biopsy results. Prostate Nov 1;37(3):140-8
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res Jan 1;30(1):412-5.