Magnetic Resonance Imaging of Therapy-induced Necrosis Using Gadolinium-Chelated Polyglutamic Acids

Edward Jackson

Emilio Esparza-Coss

Xiaoxia Wen

Chaan Ng

Sherita Daniel

Roger Price

Belinda Rivera

Chusilp Charnsangavej

Juri Gelovani

Chun Li

^{Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030}

^{Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030}

^{Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030}

^{Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030}

Requests for reprints: Chun Li, Department of Experimental Diagnostic Imaging, Unit 59, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Tel: 713-792-5182; Fax: 713-794-5456; E-mail: ude.cmt.ccadm.id@ilc

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Abstract

Purpose

Necrosis is the most common morphological alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents—gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)—in necrotic tissue.

Methods and Materials

Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T₁-weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls.

Results

Initially, there was minimal tumor enhancement following injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd but rapid enhancement following injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd co-localized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages.

Conclusions

Our data suggest that MRI with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis.

Keywords: Magnetic resonance imaging, necrosis, macrophages, polymer, treatment response

Abstract

Footnotes

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Footnotes

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