Literature DB >> 23334725

Phase 0 microdosing PET study using the human mini antibody F16SIP in head and neck cancer patients.

Derrek A Heuveling1, Remco de Bree, Danielle J Vugts, Marc C Huisman, Leonardo Giovannoni, Otto S Hoekstra, C René Leemans, Dario Neri, Guus A M S van Dongen.   

Abstract

UNLABELLED: The aim of this microdosing phase 0 clinical study was to obtain initial information about pharmacokinetics, biodistribution, and specific tumor targeting of the antitenascin-C mini antibody F16SIP.
METHODS: Two milligrams of F16SIP, labeled with 74 MBq of (124)I, were intravenously administered to patients with head and neck cancer (n = 4) scheduled for surgery 5-7 d later. Immuno-PET scans were acquired at 30 min and 24 h after injection. For pharmacokinetic analysis, blood samples were taken at different time points after infusion. Tissue uptake was extracted from whole-body PET scans. In addition, ex vivo radioactivity measurements of blood and of biopsies from the surgical specimens were performed.
RESULTS: (124)I-F16SIP was well tolerated. Uptake was visible mainly in the liver, spleen, kidneys, and bone marrow and diminished over time. Tumor uptake increased over time, with all 4 tumors visible on 24-h PET images. The tumor-to-blood ratio was 7.7 ± 1.7 at the time of surgery. Pharmacokinetic analysis revealed good bioavailability of (124)I-F16SIP.
CONCLUSION: Performing a microdosing immuno-PET study appeared feasible and demonstrated adequate bioavailability and selective tumor targeting of (124)I-F16SIP.The results of this study justify further clinical exploration of (124)I-F16SIP-based therapies.

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Year:  2013        PMID: 23334725     DOI: 10.2967/jnumed.112.111310

Source DB:  PubMed          Journal:  J Nucl Med        ISSN: 0161-5505            Impact factor:   10.057


  18 in total

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2.  De novo expression of fetal ED-A(+) fibronectin and B (+) tenascin-C splicing variants in human cardiac allografts: potential impact for targeted therapy of rejection.

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3.  PET imaging of tenascin-C with a radiolabeled single-stranded DNA aptamer.

Authors:  Orit Jacobson; Xuefeng Yan; Gang Niu; Ido D Weiss; Ying Ma; Lawrence P Szajek; Baozhong Shen; Dale O Kiesewetter; Xiaoyuan Chen
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4.  Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma.

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9.  A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo.

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Review 10.  Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions.

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Journal:  Drug Discov Today       Date:  2015-10-23       Impact factor: 7.851

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