Radiation dosimetry and first therapy results with a 124I-131I-labeled small molecule MIP-1095 targeting PSMA for prostate cancer therapyReportar como inadecuado




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European Journal of Nuclear Medicine and Molecular Imaging

, Volume 41, Issue 7, pp 1280–1292

First Online: 28 February 2014Received: 02 October 2013Accepted: 20 January 2014DOI: 10.1007-s00259-014-2713-y

Cite this article as: Zechmann, C.M., Afshar-Oromieh, A., Armor, T. et al. Eur J Nucl Med Mol Imaging 2014 41: 1280. doi:10.1007-s00259-014-2713-y

Abstract

IntroductionSince the prostate-specific membrane antigen PSMA is frequently over-expressed in prostate cancer PCa several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer mCRPC. We investigated the tissue kinetics of a small molecule inhibitor of PSMA S-2-3-S-1-carboxy-5-3-4-Iiodophenylureidopentylureidopentanedioicacid; MIP-1095 using PET-CT to estimate radiation dosimetry for the potential therapeutic use of I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of I-MIP-1095.

MethodsSixteen patients with known prostate cancer underwent PET-CT imaging after i.v. administration of I-MIP-1095 mean activity: 67.4 MBq. Each patient was scanned using PET-CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA-EXM software. Twenty-eight men with mCRPC were treated with a single cycle of I-MIP-1095 mean activity: 4.8 GBq, range 2 to 7.2 GBq and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA.

ResultsI-124-MIP-1095 PET-CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands 3.8 mSv-MBq, liver 1.7 mSv-MBq and kidneys 1.4 mSv-MBq. The absorbed dose calculated for the red marrow was 0.37 mSv-MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed.

ConclusionBased on the biodistribution and dose calculations of the PSMA-targeted small molecule I-MIP-1095 therapy with the authentic analog I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy.

KeywordsProstate cancer PSMA targeting Radioiodinated PSMA ligand Biodistribution Absorbed dose estimates Dosimetry Christian M. Zechmann and Ali Afshar-Oromieh contributed equally to the work and manuscript.

John W. Babich and Uwe Haberkorn are co-senior authors.

Electronic supplementary materialThe online version of this article doi:10.1007-s00259-014-2713-y contains supplementary material, which is available to authorized users.

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Autor: Christian M. Zechmann - Ali Afshar-Oromieh - Tom Armor - James B. Stubbs - Walter Mier - Boris Hadaschik - John Joyal - K

Fuente: https://link.springer.com/



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