Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications

Dongen, Guus A.M.S. van; Visser, Gerard W.M.; Hooge, Marjolijn N. Lub-de; Vries, Elisabeth G.E. de; Perk, Lars R.

doi:10.1634/theoncologist.12-12-1379

Cited by 294 publications

(247 citation statements)

References 47 publications

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“…In this way, not only the level of a molecular target in the tumour, but also its accessibility to proposed therapy might be evaluated [16,30,31]. However, slow clearance from blood and organs in equilibrium with blood requires several (three-to-seven) days between injection of the probe and measurement, to obtain a reasonably high tumour-to-blood ratio.…”

Section: Discussionmentioning

confidence: 99%

[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

Orlova

Hofström

Strand

et al. 2012

Eur J Nucl Med Mol Imaging

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Section: Discussionmentioning

confidence: 99%

[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

Orlova

Hofström

Strand

et al. 2012

Eur J Nucl Med Mol Imaging

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“…A common approach for molecular imaging of therapeutic targets is the use of radiolabelled antibodies [14]. Currently, a radiolabelled anti-HER3 antibody U3-1287 is in clinical trial (NCT01479023).…”

Section: Introductionmentioning

confidence: 99%

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Orlova

Malm

Rosestedt

et al. 2014

Eur J Nucl Med Mol Imaging

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Imaging of HER3-expressing xenografts in mice using a (99m)Tc(CO) 3-HEHEHE-Z HER3 08699 affibody molecule. Tc(CO) 3 -HEHEHE-Z 08699 was studied over time in mice bearing HER3-expressing xenografts. European Journal of Nuclear Medicine and MolecularResults. HEHEHE-Z 08699 was labeled with 99m Tc(CO) 3 with an isolated yield of >80% and a purity of >99%. Binding of 99m Tc(CO) 3 -HEHEHE-Z 08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of receptor/affibody molecule complex (70% cell associated radioactivity was internalized after 24 h). Tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor mediated uptake was also found in liver, lung, stomach, intestine, and salivary glands.At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions. The results of this study suggest feasibility of HER3-imaging in malignant tumors using affibody molecules.

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“…These pharmaceutical developments rely crucially on the antibody's ability to localize at sites of disease. Immuno-PET, a molecular imaging technique combining the high resolution and sensitivity of positron emission tomography (PET) and the selective localization of antibodies at their target in vivo, has profited from recent technical advances and the availability of Good Manufacturing Practice (GMP)-grade radionuclides, and might play an important role in the future both in cancer staging and tailoring of therapy (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…Although radiometals (e.g., Zr and Cu) are attached via chelators, iodine can be coupled directly with the antibodies without impacting on its pharmacokinetic properties. As iodine might be cleaved from the protein complex upon internalization, the use of 124 I is particularly attractive for noninternalizing antibodies (7,8).…”

Section: Introductionmentioning

confidence: 99%

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

Poli

Bianchi

Virotta

et al. 2013

Cancer Immunology Research

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Radioimmunotherapy (RIT) with 131 I-labeled L19SIP (radretumab; a small immunoprotein format antibody directed against the ED-B domain of fibronectin; $80 kDa molecular weight) has been investigated in several clinical trials. Here, we describe the use of immuno-PET imaging with iodine-124 ( 124 I)-labeled L19SIP to predict doses delivered to tumor lesions and healthy organs by a subsequent radretumab RIT in patients with brain metastases from solid cancer. Bone marrow doses were evaluated both during the diagnostic phase and posttherapy, measuring activities in blood (germanium detector) and whole body (lanthanum bromide detector). Expected doses for radretumab administration (4,107 MBq/m 2 ) were calculated from data obtained after administration of an average of 167 MBq 124 I-L19SIP to 6 patients. To assess lesion average doses, the positron emission tomography (PET) scanner was calibrated for the use of 124 I with an International Electrotechnical Commission (IEC) Body Phantom and recovery coefficients were calculated. The average dose to bone red marrow was 0.21 Gy/GBq, with high correlation between provisional and actual posttherapy doses. Although the fraction of injected activity in normal organs was similar in different patients, the antibody uptake in the neoplastic lesions varied by as much as a factor of 60. Immuno-PET with 124 I-labeled L19SIP offers significant advantages over conventional 131 I imaging, in particular accuracy of dosimetric results. Furthermore, the study indicates that antibody uptake can be highly variable even in different lesions of the same patient and that immuno-PET procedures may guide product development with armed antibodies. Cancer Immunol Res; 1(2); 134-43. Ó2013 AACR.

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Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications

Cited by 294 publications

References 47 publications

[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

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