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SUMMARY:123I-ADAM10 inhibitor as a new theranostic agent for cervical canc
 er
DTSTART;VALUE=DATE-TIME:20231130T124000Z
DTEND;VALUE=DATE-TIME:20231130T125500Z
DTSTAMP;VALUE=DATE-TIME:20260715T230656Z
UID:indico-contribution-3393@indico.tlabs.ac.za
DESCRIPTION:Speakers: Julie Bolcaen (Radiobiology\, Radiation Biophysics\,
  iThemba LABS\, Cape Town)\nThe aim of this study is to evaluate the suita
 bility of ADAM10 as a target for imaging cervical cancer using a 123I-radi
 olabelled ADAM10 inhibitor. A Disintegrin and Metalloproteinases (ADAMs) e
 xhibit proteolytic activity like matrix metalloproteinases and ADAM10 shed
 s a range of membrane-bound proteins that play a role in cancer progressio
 n\, radioresistance and the tumor micro-environment. First\, the therapeut
 ic and radiosensitizing effects of the non-radiolabelled ADAM10 inhibitor 
 (GI254023X\, GI) were evaluated in cervical cancer cells (Hela\, C33A). Th
 is includes effects on proliferation\, clonogenicity\, migration\, invasio
 n\, apoptosis\, DNA damage and adhesion. Preliminary results show an inhib
 ition of migration but no effect on cell cycle progression\, apoptosis\, n
 or radiosensitizing effects. Secondly\, GI was radiolabelled with Iodine-1
 23 (98% radiochemical purity\, ± 44 MBq/mL). 123I-GI is enantiomerically 
 pure with a thermal stability up to 125°C. Whole blood and protein bindin
 g studies confirmed a 34% binding to read blood cells with 66% activity lo
 cated in serum (0-1-2-24 hrs). Within the serum\, 33% was protein bound. T
 he partition coefficient indicated a lipophilicity of 0.555. Preliminary i
 n vitro studies demonstrated that 123I-GI was taken up in cervical cancer 
 cells. Blocking studies with an overdose of cold GI did not affect the upt
 ake of 123I-GI in Hela/C33A cells. The effect of 123I-GI on clonogenicity 
 of Hela/C33A cells is ongoing (auger effect). The potential of 123I-GI as 
 a cancer diagnostic agent will further be investigated using a xenograft c
 ervical cancer model. The biodistribution\, pharmacokinetics and targeting
  will be determined in vivo (µSPECT-CT and autoradiography). All these in
  vitro\, ex vivo and in vivo validations of GI and 123I-GI will give more 
 insights into the cell surface protein’s activity\, function and its rol
 e in tumorigenesis. This will set the scene for evaluating GI linked to th
 e alpha therapeutic nuclide 211At or the beta emitting 131I. This study wi
 ll be the first step in establishing a pipeline for theranostics research 
 at iThemba LABS.\n\nhttps://indico.tlabs.ac.za/event/119/contributions/339
 3/
LOCATION:
URL:https://indico.tlabs.ac.za/event/119/contributions/3393/
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