Bevacizumab Radioimmunotherapy (RIT) with Accelerated Blood Clearance Using the Avidin Chase

The overexpression of vascular endothelial growth factor (VEGF) in varying types of solid tumor renders radioimmunotherapy (RIT) with the anti-VEGF antibody bevacizumab (BV) a promising treatment. However, the slow blood clearance of BV, which may increase the occurrence risk of hematotoxicity, hinders the application of BV-RIT. Using the avidin chase is a long-known blood clearance enhancement strategy for biotinylated-mAb. To enhance RIT efficacy by increasing the radioactivity dose, we evaluated the ability of avidin to accelerate the blood clearance of yttrium-90 (⁹⁰Y)-labeled biotinylated BV (⁹⁰Y-Bt-BV) in a xenograft mouse model of triple-negative breast cancer (TNBC). The biodistribution study in the TNBC xenograft mice confirmed the high and specific tumor accumulation of the indium-111 (¹¹¹In)-BV. The blood clearance enhancement effect of the avidin chase was demonstrated in the normal mouse studies with ¹¹¹In-Bt-BV. In the subsequent biodistribution studies with the tumor-bearing mice, an optimized dose of avidin injection subsequent to ¹¹¹In-Bt-BV with an appropriate biotin valency successfully accelerated the blood clearance of ¹¹¹In-Bt-BV without impairing its tumor accumulation level. The avidin chase enabled an increase in the maximum tolerated dose of ⁹⁰Y-Bt-BV to twice as much as that of ⁹⁰Y–BV in tumor-bearing mice and thereby significantly improved the therapeutic effect of ⁹⁰Y-Bt-BV compared to ⁹⁰Y–BV (<i>p</i> < 0.05). These results underscored the potential usefulness of ⁹⁰Y-bevacizumab-RIT with the avidin chase for the treatment of VEGF-positive tumors

Percutaneous Image-Guided Biopsy for Non-Mass-Forming Isolated Splenomegaly and Suspected Malignant Lymphoma

<div><p>Background</p><p>The aim of this study was to evaluate the accuracy, safety, and role of splenic biopsy in the management of patients with non-mass-forming isolated splenomegaly and suspected malignant lymphoma.</p><p>Methods</p><p>Between 2001 and 2013, 137 biopsies were performed under computed tomography (CT) fluoroscopic guidance in 39 patients. All patients had splenomegaly based on the CT findings and a suspected diagnosis of malignant lymphoma based on their clinical symptoms. The spleen was the only accessible site to perform a biopsy, and no mass lesions could be identified in the spleen.</p><p>Results</p><p>The overall sensitivity, specificity, and diagnostic accuracy of image-guided biopsy for malignant lymphoma were 88%, 100% and 92%, respectively. Major complications occurred in 3 patients. In 1 patient, transcatheter arterial embolization was performed due to hemorrhage, and two patients needed blood transfusion because of hematoma development, without the need for further treatment.</p><p>Conclusions</p><p>Image-guided splenic core-needle biopsy is a safe and accurate technique with a high diagnostic accuracy in most patients who with non-mass-forming isolated splenomegaly and suspected underlying malignant lymphoma.</p></div

A 55-year-old woman with anemia underwent splenic biopsy.

<p>Immediately after biopsy, no obvious hematoma was observed around the spleen; however, mild hematoma formation was seen in the paracolic gutter (arrowheads).</p

A 64-year-old woman with pancytopenia underwent splenic biopsy.

<p>(a) Splenic biopsy was performed under computed tomography (CT) guidance. (b) Immediately after biopsy, contrast-enhanced CT showed a peritoneal hematoma and extravasation around the spleen (arrowhead). Transcatheter arterial embolization was immediately performed.</p

Quenched (left) and chemically dequenched (right) Pan-ICG.

<p>(A) White image (B) Fluorescence image. Dequenched conjugates showed increased fluorescence signals as shown in green.</p

Comparison of the tumor size between EGFR- and EGFR+ lymph node metastases.

<p>(A) There was no significant difference in tumor size between EGFR- and EGFR+ metastases. (B) Correlation between the fluorescence signal ratio of the lymph node metastases to liver and the size of EGFR+ lesions.</p

Flow cytometry analysis of H520 and H226 cell lines binding to Pan-ICG.

<p>In vitro cell experiment with flow cytometry showed (A) non-specific weak binding of Pan-ICG to EGFR- cell line at 6 hours and (B) specific binding of Pan-ICG to EGFR+ cell line at 6 hours.</p

Ex vivo fluorescence images of EGFR- and EGFR+ lymph node metastases.

<p>Ex vivo fluorescence images showed higher fluorescence signals in EGFR+ lymph node metastases than in EGFR- ones.</p

Pathological and immunohistochemical examinations.

<p>Comparison of the HE staining (Left) and Pan-ICG staining (Right) between EGFR- and EGFR+ lymph node metastases. Scale bar indicates 20 μm.</p

Fluorescence microscopy study of Pan-ICG binding to H520 and H226 cell lines.

<p>After 1 hour (1hr) and 6 hours (6hr) incubation, fluorescence microscopy results showed (A) no signal from EGFR- cell line (H520) and (B) weak signals at 1hr or strong signals at 6hr based on the specific binding of conjugate to EGFR+ cancer cell line (H226). Scale bar indicates 20 μm.</p