The architecture of intra-tumoral vascular network continuously evolves with tumor progression. Non-invasive methods that facilitate 3D in vivo interrogation of tumor vascular architecture could improve understanding of tumor progression and metastasis. In this work, we studied evolving tumor vasculature using high-resolution CT images and a blood-pool, nanoparticle iodinated contrast agent. In vivo studies were performed in a transgenic mouse model of neuroblastoma that exhibit spontaneous bilateral tumors in the adrenals. Animals were divided into three groups based on tumor age: early-age tumor, intermediate-age tumor, old-age tumor. Tumor progression was monitored using T2-weighted MRI. Contrast-enhanced CT imaging was performed at two points: the first imaging session (leak map) was performed 4 days after administration of the nanoparticle agent to interrogate changes in tumor vascular permeability. Immediately thereafter, a second dose of contrast agent was administered and CT imaging was performed within 1 hour to capture high-resolution angiograms of tumor vasculature. CT angiograms demonstrated the highly-vascularized nature of these tumors. Old-age tumors exhibited a higher fractional volume of avascular regions and an increased number of large superficial blood vessels on tumor periphery. Old-age tumors also demonstrated the presence of intra-vessel tumor thrombus and the invasion of tumor into the inferior vena cava. Leak maps images demonstrated signal enhancement throughout the tumor in early-age tumors, including the core region, suggestive of the presence of highly permeable blood vessels through the tumor volume. Old-age tumors exhibited relatively lower signal enhancement, indicative of a less 'leaky' tumor vascular network compared to early and intermediate-stage tumors.
Background: Cell permeable peptides (CPP) are a new class of carrier molecule to deliver biomolecules, radio-nucleotide and drugs that is gaining momentum. CPP are capable of entering into the cells by breaking the resistance of the membrane barrier and thus can be used universally in many cell types, which renders it an efficient carrier for both in-vitro and in-vivo use.
Methods: L-Maurocalcine (L-MCa), a peptide derived from scorpion venom was radiolabeled with 125I using the lactoperoxidase method. We achieved a specific activity of 45Mbq/nmole. In vitro studies with 125I-L-MCa in DAOY cells (human medulloblastoma) were studied in order to analyze the uptake of the peptide. 125I-L-MCa was injected intravenously in mice through tail vein and bio-distribution was studied using single photon emission tomography/computed tomography (SPECT/CT).
Results: The cellular uptake of the 125I-L-MCa in DAOY cells was time and dose dependent suggesting that the radiolabeled peptide retains the biological property after radiolabeling. We have observed no loss of cell viability upon uptake of 125I-L-MCa, favoring that this peptide has potential for use in in vivo studies. The distribution of the 125I-L-MCa in mice revealed its uptake in the liver, kidney and stomach. Interestingly the 125I-L-MCa was cleared from the circulation 24h post injection, thus providing another advantage for its use in in vivo studies.
Conclusions: In the present study we have shown the uptake of 125I-L-MCa in DAOY cells. Further, the 125I-L-MCa when injected in mice localized to the liver, kidney and stomach as revealed by SPECT/CT. Cells labeled with 125I-L-MCa can possibly be tracked to their target site.