Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors
10.1007/s13139-019-00587-w
- Author:
S DAUM
1
;
J P MAGNUSSON
;
L PES
;
J GARCIA FERNANDEZ
;
S CHERCHEJA
;
F. MEDDA
;
F I NOLLMANN
;
S D KOESTER
;
P PEREZ GALAN
;
A WARNECKE
;
K ABU AJAJ
;
Felix KRATZ
Author Information
1. Centurion Biopharma Corporation/CytRx Drug Discovery Branch, Engesserstr. 4, 79108 Freiburg, Germany. fkratz@centurionbiopharma.com
- Publication Type:Original Article
- From:Korean Journal of Nuclear Medicine
2019;53(3):189-198
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE:The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors.
METHODS:111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4–8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4–6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection.
RESULTS:111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7–3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2–6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h post-injection showed 1.3–2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9–9.4.
CONCLUSION:111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.
