Imaging heterogeneity of peptide delivery and binding in solid tumors using SPECT imaging and MRI

Abstract

BackgroundAs model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this solid-tumor model, high tumor uptake of targeting peptides was expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous receptor distribution in the tumor xenografts as assessed by in vitro autoradiography. We hypothesized that delivery of peptide to the tumor cells is dictated by adequate local tumor perfusion. To study this relationship, sequential SPECT/CT and MRI were performed to assess the role of vascular functionality in radiopeptide accumulation.MethodsHigh-resolution SPECT and dynamic contrast-enhanced (DCE)-MRI were acquired in six mice bearing PC295 PDX tumors expressing the gastrin-releasing peptide (GRP) receptor. Two hours prior to SPECT imaging, animals received 25 MBq 111In(DOTA-(βAla)2-JMV594) (25 pmol). Images were acquired using multipinhole SPECT/CT. Directly after SPECT imaging, MR images were acquired on a 7.0-T dedicated animal scanner. DCE-MR images were quantified using semi-quantitative and quantitative models. The DCE-MR and SPECT images were spatially aligned to compute the correlations between radioactivity and DCE-MRI-derived parameters over the tumor.ResultsWhereas histology, in vitro autoradiography, and multiple-weighted MRI scans all showed homogenous tissue characteristics, both SPECT and DCE-MRI showed heterogeneous distribution patterns throughout the tumor. The average Spearman’s correlation coefficient between SPECT and DCE-MRI ranged from 0.57 to 0.63 for the “exchange-related” DCE-MRI perfusion parameters.ConclusionsA positive correlation was shown between exchange-related DCE-MRI perfusion parameters and the amount of radioactivity accumulated as measured by SPECT, demonstrating that vascular function was an important aspect of radiopeptide distribution in solid tumors. The combined use of SPECT and MRI added crucial information on the perfusion efficiency versus radiopeptide uptake in solid tumors and showed that functional tumor characteristics varied locally even when the tissue appeared homogenous on current standard assessment techniques.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0160-4) contains supplementary material, which is available to authorized users.

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“…AUCn and SEmax ), negatively associated with HEcount. These findings match those of other studies (Figure ). If low TTP , TOP, and BE imply adequate vascular function and perfusion, and thereby delivery of 177 Lu‐octreotate, increased apoptotic activity in the affected regions can be inferred.…”

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“…Although it must be stated that these factors can play major roles in determining therapeutic efficacy and should not be disregarded without care 36 , 37 . Moreover, we have not analyzed the functionality of the vessels or investigated the perfusion efficiency in these tumors, a factor which has also proven to be of importance to delivery of radioligands 38 .…”

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