Radioimmunotherapy with Radretumab in Patients with Relapsed Hematologic Malignancies

Erba, Paola Anna; Sollini, Martina; Orciuolo, Enrico; Traino, Claudio; Petrini, Mario; Paganelli, Giovanni; Bombardieri, Emilio; Grana, Chiara Maria; Giovannoni, Leonardo; Neri, Dario; Menssen, Hans D.; Mariani, Giuliano

doi:10.2967/jnumed.111.101006

Cited by 64 publications

(56 citation statements)

References 19 publications

(21 reference statements)

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“…The image quality obtained with the immuno-PET procedure was superior to conventional SPECT scans with 131 I-labeled antibody preparations, suggesting the applicability of 124 I-labeled L19SIP for the determination of RIT dosimetries and for the noninvasive detection of L19 uptake in neoplastic lesions. Radretumab represents a well-tolerated therapeutic option, which has shown encouraging therapeutic results for treatment of patients with lymphoma (34,35) or with brain metastases of various types of cancer, in combination with whole-brain external beam radiation (manuscript in preparation). The large …”

Section: Resultsmentioning

confidence: 99%

“…The comparison of Fig. 3D and E shows that image quality and resolution was highly superior with 124 I-L19SIP immuno-PET procedures, as compared with dosimetric single photon emission computed tomography (SPECT) scans obtained with 131 I-L19SIP (34).…”

Section: Radioactive Doses To Tumor Lesions and To Healthy Organsmentioning

confidence: 99%

“…L19SIP (Philogen S.p.A) was radioiodinated at Azienda Ospedaliera Papa Giovanni XXIII, using a modified chloramine-T method, as described previously (34,35). Briefly, 4 mg of L19SIP were labeled with about 370 MBq of 124 I-iodide [produced by the Advanced Center Oncology Macerata (ACOM), Montecosaro, Macerata, Italy) or 7.4 GBq of 131 I-iodide (GE Healthcare; about 25 mg of chloramine-T for 4 mg of L19SIP; 3-minute reaction time) and purified with a Hiprep 26/10 Desalting Column (GE Healthcare).…”

Section: L19sip Antibody and Radiolabelingmentioning

confidence: 99%

“…as defined by PET) and with a provisional dose to the bone red marrow less than 2 Gy, were then treated with 4,107 MBq/m 2 (111 mCi/m 2 ) of 131 I-radretumab ($4.2 mg of protein). Although the calculation of provisional doses derived from dosimetric 131 I-L19SIP administration has been reported (34,35), here we describe a methodology to accurately determine the expected radretumab RIT doses to the bone red marrow, lesions, and healthy organs after dosimetric administration of 124 I-L19SIP, which was applied to 6 patients in the above-mentioned trial. The study not only indicates that immuno-PET with 124 I-labeled L19SIP allows the determination of accurate dosimetries for radioimmunotherapeutic treatment with 131 I-labeled L19SIP, but it also identifies an unsuspected variability of antibody-uptake in different lesions, even within the same patient.…”

Section: Introductionmentioning

confidence: 99%

“…The molecular weight of L19-SIP in its nonreduced form is approximately 80 kDa. RIT with 131 I-labeled L19SIP (radretumab) has been investigated in a phase I and a subsequent phase I/II dose-finding and efficacy study in patients with a variety of cancers, where 131 I-L19SIP has shown excellent tolerability at radioactive doses as high as 7,400 MBq (200 mCi) with therapeutic benefit for some patients enrolled in the study (34,35). This phase II proofof-concept study (EudraCT no.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Radioactive Doses To Tumor Lesions and To Healthy Organsmentioning

confidence: 99%

Section: L19sip Antibody and Radiolabelingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Human fibronectin extra domain B as a biomarker for targeted therapy in cancer

et al. 2020

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The extracellular matrix protein fibronectin contains a domain that is rarely found in healthy adults and is almost exclusively expressed by newly formed blood vessels in tumours, particularly in solid tumours, different types of lymphoma and some leukaemias. This domain, called the extra domain B (ED-B), thus has broad therapeutic potential. The antibody L19 has been developed to specifically target ED-B and has shown therapeutic potential when combined with cytokines, such as IL-2. In this review article, we discuss the preclinical research and clinical trials that highlight the potential of ED-B targeting for the imaging and treatment of various types of cancer. ED-B-centred studies also highlight how proper patient stratification is of utmost importance for the successful implementation of novel antibody-based targeted therapies.

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Aligning physics and physiology: Engineering antibodies for radionuclide delivery

Tsai

2018

Labelled Comp Radiopharmac

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The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell surface targets in oncology and immunology. Protein engineering has been used for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance. Although intact antibodies have high potential as imaging and therapeutic agents, challenges include long circulation time in blood, which leads to later imaging time points post-injection and higher blood absorbed dose that may be disadvantageous for RIT. Using engineered fragments may address these challenges, as size reduction and removal of Fc function decreases serum half-life. Radiolabeled fragments and pretargeting strategies can result in high contrast images within hours to days, and a reduction of RIT toxicity in normal tissues. Additionally, fragments can be engineered to direct hepatic or renal clearance, which may be chosen based on the application and disease setting. This review discusses aligning the physical properties of radionuclides (positron, gamma, beta, alpha, and Auger emitters) with antibodies and fragments and highlights recent advances of engineered antibodies and fragments in preclinical and clinical development for imaging and therapy.

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Radioimmunotherapy with Radretumab in Patients with Relapsed Hematologic Malignancies

Cited by 64 publications

References 19 publications

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

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

Human fibronectin extra domain B as a biomarker for targeted therapy in cancer

Aligning physics and physiology: Engineering antibodies for radionuclide delivery

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