Differentiating Between Cancer and Inflammation: A Metabolic-Based Method for Functional Computed Tomography Imaging

One of the main limitations of the highly used cancer imaging technique, PET-CT, is its inability to distinguish between cancerous lesions and post treatment inflammatory conditions. The reason for this lack of specificity is that [¹⁸F]­FDG-PET is based on increased glucose metabolic activity, which characterizes both cancerous tissues and inflammatory cells. To overcome this limitation, we developed a nanoparticle-based approach, utilizing glucose-functionalized gold nanoparticles (GF-GNPs) as a metabolically targeted CT contrast agent. Our approach demonstrates specific tumor targeting and has successfully distinguished between cancer and inflammatory processes in a combined tumor-inflammation mouse model, due to dissimilarities in angiogenesis occurring under different pathologic conditions. This study provides a set of capabilities in cancer detection, staging and follow-up, and can be applicable to a wide range of cancers that exhibit high metabolic activity

Program code.

(DOCX)</p

Whisker plot of linear/parallel ratios of nine malignancies including the outliers of each tumor.

Whisker plot of linear/parallel ratios of nine malignancies including the outliers of each tumor.</p

Representative chest CT scans of patients with lung metastases.

Patients with melanomas, sarcomas, colorectal, bladder and breast cancers typically show variable diameters of metastases, while patients with pancreas, prostate, kidney, and thyroid cancers typically show metastases of similar diameters.</p

Examples of metastases diameter distribution in various diseases.

A. an 82-year-old man with pancreatic tumor and 25 metastases. Four waves of metastases are seen LPR = 1. B. a 66-year-old man with leiomyosarcoma. Fourteen metastases are depicted with very limited similarity in diameters. LPR = -0.43. C. a 72-year-old man with colorectal carcinoma and 28 metastases. Some of the metastases can be clustered and some cannot, LPR = 0.57. D. a 72-year-old man with melanoma. Thirty-three metastases are depicted. Six to seven waves of metastases can be seen. LPR = 0.82.</p

The complete data set.

(XLS)</p

Outcome of patients with lung metastases.

(DOCX)</p

Basic parameters of patients with lung metastases.

(DOCX)</p

Measurements of the metastases and their linear/parallel ratio (LPR).

Measurements of the metastases and their linear/parallel ratio (LPR).</p

Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T‑Cells <i>in Vivo</i> with Gold Nanoparticles and CT Imaging

Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative <i>in vivo</i> cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced cells. Labeling with gold nanoparticles did not affect T-cell function, as demonstrated both <i>in vitro</i>, by cytokine release and proliferation assays, and <i>in vivo</i>, as tumor regression was observed. Moreover, to validate the accuracy and reliability of the proposed cell tracking technique, T-cells were labeled both with green fluorescent protein for fluorescence imaging, and with GNPs for CT imaging. A remarkable correlation in signal intensity at the tumor site was observed between the two imaging modalities, at all time points examined, providing evidence for the accuracy of our CT cell tracking abilities. This new method for cell tracking with CT offers a valuable tool for research, and more importantly for clinical applications, to study the fate of immune cells in cancer immunotherapy