Preclinical evaluation of a monoclonal antibody targeting the epidermal growth factor receptor as a radioimmunodiagnostic and radioimmunotherapeutic agent

Ray, Geoffrey L.; Baidoo, K E; Wong, K.J.; Williams, Mark R.; Garmestani, Kayhan; Brechbiel, M. W.; De, Milenic

doi:10.1111/j.1476-5381.2009.00327.x

Cited by 24 publications

(52 citation statements)

References 27 publications

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“…For 125 I-labeled panitumumab and trastuzumab, the radiochemical yields ranged from 50% to 60%, with a specific activity of approximately 1GBq/ mg. The I-labeled antibodies demonstrated total cell binding of over 75% and specific cell binding of over 90%, as previously described (18,19).…”

Section: Radioimmunochemistrysupporting

confidence: 69%

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Orthotopic Pleural Mesothelioma in Mice: SPECT/CT and MR Imaging with HER1- and HER2-targeted Radiolabeled Antibodies

Nayak

Bernardo²,

Milenic³

et al. 2013

Radiology

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Purpose:To evaluate the potential of anti-human epidermal growth factor receptor (HER)1-and anti-HER2-targeted radiolabeled antibodies and magnetic resonance (MR) imaging for imaging of orthotopic malignant pleural mesothelioma (MPM) in mouse models. Materials and Methods:Animal studies with 165 mice were performed in accordance with National Institutes of Health guidelines for the humane use of animals, and all procedures were approved by the institutional Animal Care and Use Committee. Flow cytometry studies were performed to evaluate HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Biodistribution and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies were performed in mice (four or five per group, depending on tumor growth) bearing subcutaneous and orthotopic MPM tumors by using HER1-and HER2-targeted indium 111 ( 111 In)-and iodine 125 ( 125 I)-labeled panitumumab and trastuzumab, respectively. Longitudinal MR imaging over 5 weeks was performed in three mice bearing orthotopic tumors to monitor tumor growth and metastases. SPECT/CT/MR imaging studies were performed at the final time point in the orthotopic models (n = 3). The standard unpaired Student t test was used to compare groups. Results:Orthotopic tumors and pleural effusions were clearly visualized at MR imaging 3 weeks after tumor cell inoculation. At 2 days after injection, the mean 111 In-panitumumab uptake of 29.6% injected dose (ID) per gram 6 2.2 (standard error of the mean) was significantly greater than the 111 In-trastuzumab uptake of 13.6% ID/g 6 1.0 and the 125 Ipanitumumab uptake of 7.4% ID/g 6 1.2 (P = .0006 and P = .0001, respectively). MR imaging fusion with SPECT/CT provided more accurate information about 111 In-panitumumab localization in the tumor, as the tumor was poorly visualized at CT alone. Conclusion:This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of MPM in preclinical models.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

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Section: Radioimmunochemistrysupporting

confidence: 69%

“…Panitumumab and trastuzumab were conjugated with the bifunctional chelator CHX-A0-DTPA as previously described (18,19). Radiolabeling and quality control of iodine 125 ( Intrastuzumab conjugates were performed as previously described (11,19).…”

Section: Preparation Of Radioimmunoconjugatesmentioning

confidence: 99%

Orthotopic Pleural Mesothelioma in Mice: SPECT/CT and MR Imaging with HER1- and HER2-targeted Radiolabeled Antibodies

Nayak

Bernardo²,

Milenic³

et al. 2013

Radiology

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“…56 Briefly, EGFR was allowed to adsorb to the wells of a 96-well plate, the EGFR was removed and 1% bovine serum albumin in phosphate buffered saline (BSA/PBS; 100 mL) was added to each well. Following a 0.5-1 h incubation at room temperature, the solution was removed and serial dilutions of the immunoconjugate (500 to 0.01 ng in 25 mL) in BSA/PBS were added to the wells in triplicate.…”

Section: Radioimmunoassaysmentioning

confidence: 99%

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

Milenic

Baidoo

Kim

et al. 2015

mAbs

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“…For the synthesis of the 111 In-CHX-A″-DTPA-panitumumab, 111 In was purchased from Perkin-Elmer, Waltham, MA. 111 In-CHX-A″-DTPA-panitumumab was prepared following the literature procedure (21). …”

Section: Methodsmentioning

confidence: 99%

“…The immunoreactivity assay was performed with MDA-MB-468 cells following the procedure described in the literature (19, 21). Serial dilution of 89 Zr-DFO-panitumumab (30,000 – 200,000 cpm in 50 μL of BSA/PBS) were added to 12 × 17 mm test tube containing MDA-MB-468 cells (1.1 × 10 6 in 50 μL of BSA/PBS).…”

Section: Methodsmentioning

confidence: 99%

Zirconium-89 labeled panitumumab: a potential immuno-PET probe for HER1-expressing carcinomas

Bhattacharyya

Kurdziel

Wei

et al. 2013

Nuclear Medicine and Biology

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Introduction Anti-HER1 monoclonal antibody (mAb), panitumumab (Vectibix®) is a fully human mAb approved by the FDA for the treatment of epidermal growth factor receptor (EGFR, HER1)-expressing colorectal cancers. By combining the targeted specificity of panitumumab with the quantitative in vivo imaging capabilities of PET, we evaluated the potential of 89Zr-DFO-panitumumab PET/CT imaging and performed non-invasive, in vivo imaging of HER1 expression and estimated human dosimetry. Methods Panitumumab was radiolabeled with 89Zrusing a derivative of desferrioxamine (DFO-Bz-NCS) and with 111In using CHX-A″ DTPA as bifunctional chelators. Comparative biodistribution/dosimetry of both radiotracers was performed in non-tumor bearing athymic nude mice (n= 2 females and n=2 males) over 1-week following i.v. injection of either using 89Zr-DFO-panitumumab or 111In-CHX-A″-DTPA-panitumumab. Micro-PET/CT imaging of female athymic nude mice bearing human breast cancer tumors (n=5 per tumor group) with variable HER1-expression very low (BT-474), moderate (MDA-MB-231), and very high (MDA-MB-468) was performed at over 1 week following i.v. injection of 89Zr-DFO-panitumumab. Results Radiochemical yield and purity of 89Zr-Panitumumab was > 70% and > 98% respectively with specific activity 150 ± 10 MBq/mg of panitumumab in a ~ 4 hr synthesis time. Biodistribution of 111In-CHX-A″ DTPA -panitumumab and 89Zr-DFO-panitumumab in athymic non-tumor bearing nude mice displayed similar percent injected dose per gram of tissue with prominent accumulation of both tracers in the lymph nodes, a known clearance mechanism of panitumumab. Also exhibited was prolonged blood pool with no evidence of targeted accumulation in any organ. Human radiation dose estimates showed similar biodistributions with estimated human effective doses of 0.578 and 0.183 mSv/MBq for 89Zr-DFO-panitumumab and 111In-CHX-A″-DTPA –panitumumab, respectively. Given the potential quantitative and image quality advantages of PET, imaging of tumor bearing mice was only performed using 89Zr-DFO-panitumumab. Immuno-PET imaging of 89Zr-DFO-panitumumab in mice bearing breast cancer xenograft tumors with variable HER1 expression showed high tumor uptake (SUV > 7) in the MDA-MB-468 high HER1-expressing mice and a strong correlation between HER1-expression level and tumor uptake (R2= 0.857, p<0.001). Conclusions 89Zr-DFO-panitumumab can prepared with high radiochemical purity and specific activity. 89Zr-DFO-panitumumab microPET/CT showed uptake corresponding to HER-1 expression. Due to poor clearance, initial dosimetry estimates suggest that only a low dose 89Zr-DFO-panitumumab shows favorable human dosimetry; however due to high tumor uptake, the use of 89Zr-DFO-panitumumab is expected to be clinically feasible.

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Preclinical evaluation of a monoclonal antibody targeting the epidermal growth factor receptor as a radioimmunodiagnostic and radioimmunotherapeutic agent

Cited by 24 publications

References 27 publications

Orthotopic Pleural Mesothelioma in Mice: SPECT/CT and MR Imaging with HER1- and HER2-targeted Radiolabeled Antibodies

Orthotopic Pleural Mesothelioma in Mice: SPECT/CT and MR Imaging with HER1- and HER2-targeted Radiolabeled Antibodies

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

Zirconium-89 labeled panitumumab: a potential immuno-PET probe for HER1-expressing carcinomas

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