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Title: Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC

Abstract

The radiotracer called {sup 68}Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) is a novel radiophar-maceutical for the detection of prostate cancer lesions by positron emission tomography (PET) imaging. Setting up a cost-effective manual synthesis of this radiotracer and making its clinical translation in Colombia will require two important elements: the evaluation of the procedure to yield a consistent product, meeting standards of radio-chemical purity and low toxicity and then, the evaluation of the radiation dosimetry. In this paper a protocol to extrapolate the biokinetic model made in normal mice to humans by using the computer software for internal dose assessment OLINDA/EXM® is presented as an accurate and standardized method for the calculation of radiation dosimetry estimates.

Authors:
;  [1]
  1. Grupo de Física Nuclear, Departamento de Física, Universidad Nacional de Colombia, Bogota, D.C. (Colombia)
Publication Date:
OSTI Identifier:
22608529
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 1753; Journal Issue: 1; Conference: Latin American symposium on nuclear physics and applications, Medellin (Colombia), 30 Nov - 4 Dec 2015; Other Information: (c) 2016 Author(s); Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOMEDICAL RADIOGRAPHY; DETECTION; DOSIMETRY; EMISSION; GALLIUM 68; HUMAN POPULATIONS; IMPURITIES; NEOPLASMS; POSITRON COMPUTED TOMOGRAPHY; POSITRONS; PROSTATE; RADIOPHARMACEUTICALS; SYNTHESIS; TOXICITY; TRACER TECHNIQUES; UREA

Citation Formats

Parra, Pamela Ochoa, E-mail: lapochoap@unal.edu.co, and Veloza, Stella. Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC. United States: N. p., 2016. Web. doi:10.1063/1.4955383.
Parra, Pamela Ochoa, E-mail: lapochoap@unal.edu.co, & Veloza, Stella. Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC. United States. doi:10.1063/1.4955383.
Parra, Pamela Ochoa, E-mail: lapochoap@unal.edu.co, and Veloza, Stella. 2016. "Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC". United States. doi:10.1063/1.4955383.
@article{osti_22608529,
title = {Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC},
author = {Parra, Pamela Ochoa, E-mail: lapochoap@unal.edu.co and Veloza, Stella},
abstractNote = {The radiotracer called {sup 68}Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) is a novel radiophar-maceutical for the detection of prostate cancer lesions by positron emission tomography (PET) imaging. Setting up a cost-effective manual synthesis of this radiotracer and making its clinical translation in Colombia will require two important elements: the evaluation of the procedure to yield a consistent product, meeting standards of radio-chemical purity and low toxicity and then, the evaluation of the radiation dosimetry. In this paper a protocol to extrapolate the biokinetic model made in normal mice to humans by using the computer software for internal dose assessment OLINDA/EXM® is presented as an accurate and standardized method for the calculation of radiation dosimetry estimates.},
doi = {10.1063/1.4955383},
journal = {AIP Conference Proceedings},
number = 1,
volume = 1753,
place = {United States},
year = 2016,
month = 7
}
  • This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examplesmore » and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories.« less
  • Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a 177Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401). The radiolabeling of CTT1401 and CTT1403 was achieved using click chemistrymore » to connect 177Lu-DOTA-N3 to the dibenzocyclooctyne (DBCO)-bearing CTT1298 inhibitor cores. A direct comparison in vitro and in vivo performance was made for CTT1401 and CTT1403; the specificity and efficacy by means of cellular uptake and internalization, biodistribution, and therapeutic efficacy were determined for both compounds. And while both compounds displayed excellent uptake and rapid internalization in PSMA+ PC3-PIP cells, the albumin binding moiety in CTT1403 conferred clear advantages to the PSMA-inhibitor scaffold including increased circulating half-life and prostate tumor uptake that continued to increase up to 168 h post-injection. This then increased tumor uptake translated into superior therapeutic efficacy of CTT1403 in PSMA+ PC3-PIP human xenograft tumors.« less
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  • The anti-human, high molecular weight-melanoma associated antigen (HMW-MAA)MoAb 225.28S was chelated with /sup 111/In and then tested for its in vitro reactivity with cultured human melanoma cells and for its biodistribution in human melanoma bearing nude mice. In vitro studies showed that the radiolabeled antibody reacted specifically with cultured melanoma cells. However, binding of DTPA to the monoclonal antibody reduced its titer with cultured melanoma cells from 1:1024 to 1:512. Injection of the radiolabeled monoclonal antibody into nude mice resulted in the accumulation of significantly higher radioactivity in melanoma tissue than in nude mice injected with either (/sup 111/In)chloride ormore » /sup 111/In-labeled antibody to human acid phosphatase. The localization of antibody in liver and kidney was also high, although lower than that achieved in tumor. These results indicate that /sup 111/In-labeled monoclonal antibodies to human tumor associated antigens may be useful for localizing malignant lesions. However, there is a need to improve labeling and/or purification of antibody in order to decrease renal and hepatic activity.« less