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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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111In-Benzyl-diethylenetriamine pentaacetic acid-AMB8LK

111In-DTPA-AMB8LK
, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: February 1, 2007.

Chemical name:111In-Benzyl-diethylenetriamine pentaacetic acid-AMB8LK
Abbreviated name:111In-Bz-DTPA-AMB8LK, 111In-DTPA-AMB8LK
Synonym:
Agent Category:Antibody
Target:Ferritin
Target Category:Antibody binding
Method of detection:SPECT, gamma planar
Source of signal:111In
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents

Click on protein, nucleotide (RefSeq), and gene for more information about ferritin.

Background

[PubMed]

Ferritin is an iron storage protein with a molecular mass of 440 kDa and is overexpressed in some tumors such as breast cancer (1, 2), Hodgkin's lymphoma (3), and pancreatic cancer (4, 5). Iron has the ability to promote neoplastic cell growth (6). Radiolabeled polyclonal anti-ferritin antibodies have been shown to have anti-tumor effects in patients with Hodgkin’s lymphoma. However, the response rate was dependent on the batches of polyclonal antibody used. Therefore, AMB8LK, a murine IgG1 monoclonal antibody (mAb) against ferritin extracted from human spleen with an affinity constant (Kd) of 5.1 nM, was conjugated with 111In via the bifunctional linker benzyl-diethylenetriamine pentaacetic acid (Bz-DTPA). 111In-DTPA-AMB8LK is being evaluated for imaging of pancreatic cancer (7).

Synthesis

[PubMed]

AMB8LK mAb was conjugated to 2-(4-isothiocyanatobenzyl)-diethylenetriamine pentaacetic acid (PSCN-Bz-DTPA) at 37°C overnight (7). Bz-DTPA-AMB8LK was purified by ultrafiltration. There are ~2 DTPA per mAb. BZ-DTPA-AMB8LK (0.05 mg) was mixed with 6.5 MBq (0.18 mCi) of 111InCl3 .The mixture was incubated for 30 min at room temperature. The labeling efficiency was ~95% of 111In incorporation. Specific activities of the preparations were >6 GBq/μmol (0.16 Ci/μmol).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

In vitro binding tests showed that immunoreactivity to ferritin of 111In-DTPA-AMB8LK was ~87% (7). The immunoreactivity to ferritin on human pancreatic ductal adenocarcinoma CAPAN-1 cells (fixed and permeabilized) was ~52%. 111In-DTPA-AMB8LK lost <3% of activity in plasma at 37°C for 7 days.

Animal Studies

Rodents

[PubMed]

Sabbah et al. (7) monitored biodistribution after injection of 0.2 MBq (5.4 μCi) 111In-DTPA-AMB8LK in normal nude mice (n = 4/group). Of all organs, the liver showed the highest 111In-DTPA-AMB8LK uptake of 7.0% injected dose/g (ID/g) at 24 h, 7.1% at 48 h, and 7.5% at 72 h. Other organs that showed significant levels of uptake were the bones (1.7–2.1% ID/g) and intestine (2.9–3.2% ID/g). Uptake in the muscle, lung, and kidneys was <2%, and uptake in the stomach and spleen was <1%. Radioactivity in the blood was 15.8% ID/g at 24 hr and 12.6% ID/g at 72 h. In a second series of experiments, biodistribution of 111In- DTPA-AMB8LK via injection (0.2 MBq (5.4 μCi)) was studied in nude mice (n = 4/group) bearing human pancreatic ductal adenocarcinoma CAPAN-1 xenografts at 24, 48, and 72 h. In addition to the organs analyzed during the experiments in normal mice, radioactivity levels in the tumor and pancreas were measured. Tumor uptake of 111In-DTPA-AMB8LK was 12.8% ID/g at 24 h and 23.6% at 72 h. The accumulation of radioactivity in the pancreas was <0.2% ID/g at all time points. Uptake in other organs was similar in the normal mice. Single-photon emission computed tomography imaging of a mouse bearing a CAPAN-1 tumor revealed that the majority of radioactivity was in the urinary bladder and heart, followed by the liver and lung at 1 h. The tumor was clearly visualized at 24 h with some 111In- DTPA-AMB8LK still visualized in the heart and liver. Radioactivity was still present at 72 h in the tumor but not in the heart and liver. No blocking experiment was performed.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Guner G. , Kirkali G. , Yenisey C. , Tore I.R. Cytosol and serum ferritin in breast carcinoma. Cancer Lett. 1992;67(2-3):103–12. [PubMed: 1483258]
2.
Weinstein R.E. , Bond B.H. , Silberberg B.K. , Vaughn C.B. , Subbaiah P. , Pieper D.R. Tissue ferritin concentration and prognosis in carcinoma of the breast. Breast Cancer Res Treat. 1989;14(3):349–53. [PubMed: 2611407]
3.
Eshhar Z. , Order S.E. , Katz D.H. Ferritin, a Hodgkin's disease associated antigen. Proc Natl Acad Sci U S A. 1974;71(10):3956–60. [PMC free article: PMC434305] [PubMed: 4139706]
4.
Drysdale J.W. , Adelman T.G. , Arosio P. , Casareale D. , Fitzpatrick P. , Harzard J.T. , Yokota M. Human isoferritins in normal and disease states. Semin Hematol. 1977;14(1):71–88. [PubMed: 188201]
5.
Marcus D.M. , Zinberg N. Isolation of ferritin from human mammary and pancreatic carcinomas by means of antibody immunoadsorbents. Arch Biochem Biophys. 1974;162(2):493–501. [PubMed: 4210077]
6.
Weinberg E.D. The role of iron in cancer. Eur J Cancer Prev. 1996;5(1):19–36. [PubMed: 8664805]
7.
Sabbah E.N. , Kadouche J. , Ellison D. , Finucane C. , Decaudin D. , Mather S.J. In vitro and in vivo comparison of DTPA- and DOTA-conjugated antiferritin monoclonal antibody for imaging and therapy of pancreatic cancer. Nucl Med Biol. 2007;34(3):293–304. [PubMed: 17383579]

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