NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

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

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

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

Show details

111In-Labeled panitumumab, a fully human monoclonal antibody directed against the extracellular domain III of the epidermal growth factor receptor

[111In]-Panitumumab
, PhD
National Center for Biotechnology Information, NLM, Bethesda, MD 20894

Created: ; Last Update: June 21, 2012.

Chemical name:111In-Labeled panitumumab, a fully human monoclonal antibody directed against the extracellular domain III of the epidermal growth factor receptor
Abbreviated name:[111In]-Panitumumab
Synonym:
Agent Category:Antibody
Target:Epidermal growth factor receptor (EGFR) extracellular domain III
Target Category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT); gamma planar imaging
Source of signal / contrast:111In
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Structure not available in PubChem.

Background

[PubMed]

Panitumumab is a fully human anti-epidermal factor receptor (EGFR) monoclonal antibody (mAb) that has been approved by the United States Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancers that express the EGFR and are unresponsive to chemotherapy (1). This mAb has a very high affinity for the extracellular domain III of the EGFR. The general characteristics of panitumumab have been described by Argiles et al. (2), and its mode of action has been illustrated by Dubois and Cohen (1). The fully human mAb has been reported to be well tolerated by individuals, slows disease progression, and improves the progression-free survival of patients (3). Therefore, [111In]-labeled panitumumab ([111In]-panitumumab) was evaluated for the noninvasive detection of EGFR-positive tumors in an effort to screen for patients who would benefit from radioimmunotherapy with this mAb after it was labeled with a suitable radionuclide (3). The 111In-labeled mAb was studied in vitro, and the biodistribution of [111In]-panitumumab was investigated in athymic mice bearing xenograft tumors generated with A431, HT-29, LS-174T, SHAW (obtained from the National Cancer Institute), and SKOV-3 cell lines, respectively (3). In addition, gamma scintigraphic images were acquired from mice bearing xenograft tumors to confirm noninvasive visualization of the lesions.

Synthesis

[PubMed]

The source of panitumumab was not disclosed, and the mAb was conjugated with diethylenetriamine pentaacetic acid (CHX-A''-DTPA), a bifunctional chelating agent, for labeling with 111In (3). The CHX-A''-DTPA:mAb ratio was reported to be 1.6. The radiochemical yield of the labeling reaction was 68.7 ± 12.3%, and the specific activity of the labeled mAb was 721.5 ± 329.3 MBq/66.6 nmol (19.5 ± 8.9 mCi/66.6 nmol). The radiochemical purity, stability, and formulation of the final [111In]-panitumumab preparation was not reported (3).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

A flow cytometric assay showed that the A431, HT-29, LS-174T, SHAW, and SKOV-3 cells expressed the EGFR (3). Using a competition radioimmunoassay (RIA) with [125I]-panitumumab as the ligand, the immunoreactivity of the panitumumab-CHX-A''-DTPA conjugate was shown to be similar to that of the native mAb (3). Exposure of A431 cells to [111In]-panitumumab showed that 74 ± 7.5% of the total radioactivity added to the assay was bound to the cells (3). Addition of 66.6 nmol nonradioactive panitumumab to the assay mixture resulted in only 4.0 ± 0.9% of radioactivity binding to the cells. This indicated that [111In]-panitumumab had a binding specificity for the EGFR.

Animal Studies

Rodents

[PubMed]

The biodistribution of [111In]-panitumumab was investigated in normal athymic mice (without tumors) and athymic mice bearing A431 cell tumors, as described by Ray et al. (3). The animals were injected with ~0.28 MBq (~7.5 μCi) [111In]-panitumumab through the tail vein, and the rodents (n = 5 mice/time point) were euthanized at 24, 48, 72, 96, and 168 h postinjection (p.i.) to harvest the major organs, including the tumors, to determine the uptake of radioactivity in the different tissues. Results obtained from this study were presented as percent of injected dose per milliliter (% ID/mL). In the normal mice, maximum radioactivity was observed in the salivary glands at 96 h p.i. (~15.0% ID/mL), followed by the liver at 24 h p.i. (~8.0% ID/mL), the gall bladder at 72 h p.i. (~7.5% ID/mL), and the lungs at 48 h p.i. (~7.0% ID/mL). The mice with tumors showed maximum accumulation of radioactivity in the tumor at 96 h p.i. (~17.0% ID/mL), followed by the brain at 24 h p.i. (~7.5% ID/mL), the salivary glands at 48 h p.i. (~6.5% ID/mL), and the kidneys at 24 h p.i. (~6.0% ID/mL). All other organs from the mice bearing tumors showed uptake values of <5.0% ID/mL at the various time points. No blocking studies were reported.

The biodistribution of [111In]-panitumumab was also studied in athymic mice bearing subcutaneous xenograft tumors (n = 5 animals/time point per tumor type) of HT-29 cells, LS-174T cells, SHAW cells, and SKOV-3 cells, respectively (3). Maximum uptake of label was observed in the tumor tissues of all the tumor models. Among the tumor types, the LS-174T cell human colon carcinoma xenograft tumors showed the highest accumulation of radioactivity (44.08 ± 9.53% ID/mL at 48 h p.i.). No blocking studies were reported.

For gamma scintigraphy, mice bearing xenograft tumors derived from the various cell lines were injected with 3–3.7 MBq (80–100 μCi) [111In]-panitumumab, and images were acquired from the animals at various time points from 24 h p.i. to 168 h p.i (3). The images showed that the tumors were clearly visible within 48 h p.i. Among the tumors, the LS-174T cell lesions remained visible for up to 168 h p.i (3). From the images it was apparent that high amounts of the label were present in the blood, heart, lung, and liver at 24 h p.i., and the radioactivity subsequently cleared from these tissues over the next week. No blocking studies were reported.

Results obtained from the various studies indicated that [111In]-panitumumab was a suitable tracer for the detection of tumors that express the EGFR in rodents (3).

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.

Supplemental Information

[Disclaimers]

No information is currently available.

NIH Support

Work presented in this chapter was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the Center for Cancer Research.

References

1.
Dubois E.A., Cohen A.F. Panitumumab. Br J Clin Pharmacol. 2009;68(4):482–3. [PMC free article: PMC2780272] [PubMed: 19843050]
2.
Argiles G., Dienstmann R., Elez E., Tabernero J. Panitumumab: a summary of clinical development in colorectal cancer and future directions. Future Oncol. 2012;8(4):373–89. [PubMed: 22515440]
3.
Ray G.L., Baidoo K.E., Wong K.J., Williams M., Garmestani K., Brechbiel M.W., Milenic D.E. Preclinical evaluation of a monoclonal antibody targeting the epidermal growth factor receptor as a radioimmunodiagnostic and radioimmunotherapeutic agent. Br J Pharmacol. 2009;157(8):1541–8. [PMC free article: PMC2765311] [PubMed: 19681874]
PubReader format: click here to try

Views

  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this page (578K)
  • MICAD Summary (CSV file)

Search MICAD

Limit my Search:


Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed

Related citations in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...