Dataset Information

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

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.

SUBMITTER: Daum S

PROVIDER: S-EPMC6554392 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

Daum S S Magnusson J P JP Pes L L Garcia Fernandez J J Chercheja S S Medda F F Nollmann F I FI Koester S D SD Perez Galan P P Warnecke A A Abu Ajaj K K Kratz Felix F

Nuclear medicine and molecular imaging 20190220 3

<h4>Purpose</h4>The purpose of this study was to investigate the albumin-binding compound <sup>111</sup>In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors.<h4>Methods</h4><sup>111</sup>In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, <i>n</i> = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studi ...[more]

PMID: 31231439

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Project description:ObjectivesCompanion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer.Materials and methodsThe institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study.ResultsLiposomal-I resulted in significant (p < 0.05) enhancement and uniform opacification of the vascular compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan.ConclusionsThe long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of naturally occurring canine tumors.

Dataset Information

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

Purpose

Methods

Results

Conclusion

Publications

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

Similar Datasets

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