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Model of Intraperitoneal Targeted α-Particle Therapy Shows That Posttherapy Cold-Antibody Boost Enhances Microtumor Radiation Dose and Treatable Tumor Sizes.

Artikel i vetenskaplig tidskrift
Författare Stig Palm
Tom Bäck
Sture Lindegren
Ragnar Hultborn
Lars Jacobsson
Per Albertsson
Publicerad i Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volym 59
Nummer/häfte 4
Sidor 646-651
ISSN 1535-5667
Publiceringsår 2018
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Sidor 646-651
Språk en
Länkar dx.doi.org/10.2967/jnumed.117.20128...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Radiofysik

Sammanfattning

Intraperitoneally administered radiolabeled monoclonal antibodies (mAbs) have been tested in several clinical trials, often with promising results, but have never proven curative. Methods: We have previously presented simulations of clinically relevant amounts of intraperitoneal 90Y-mAbs for treatment of minimal disease and shown that such treatments are unlikely to eradicate microtumors. Our previous model simulated the kinetics of intraperitoneally infused radiolabeled mAbs in humans and showed the benefit of instead using α-emitters such as 211At. In the current work, we introduce penetration of mAbs into microtumors with radii of up to 400 μm. Calculations were performed using dynamic simulation software. To determine the radiation dose distribution in nonvascularized microtumors of various sizes after intraperitoneal 211At-radioimmunotherapy, we used an in-house-developed Monte Carlo program for microdosimetry. Our aim was to find methods that optimize the therapy for as wide a tumor size range as possible. Results: Our results show that high-specific-activity radiolabeled mAbs that are bound to a tumor surface will penetrate slowly compared with the half-lives of 211At and shorter-lived radionuclides. The inner-core cells of tumors with radii exceeding 100 μm may therefore not be sufficiently irradiated. For lower specific activities, the penetration rate and dose distribution will be more favorable for such tumors, but the dose to smaller microtumors and single cells will be low. Conclusion: Our calculations show that the addition of a boost with unlabeled mAb 1-5 h after therapy results in sufficient absorbed doses both to single cells and throughout microtumors up to approximately 300 μm in radius. This finding should also hold for other high-affinity mAbs and short-lived α-emitters.

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