Renee Leveille

Evaluation of systemically administered radiolabeled epidermal growth factor as a brain tumor targeting agent

We have previously reported a method for labeling epidermal growth factor (EGF) with technetium-99m and have shown that 99mTc-EGF localized in EGF receptor (R) positive intracerebral C6EGFR rat gliomas following intratumoral (i.t.) injection of the radioligand. In the present study, we have evaluated the potential use of 99mTc-EGF as a tumor targeting agent after systemic administration to Fischer rats bearing intracerebral implants of C6EGFR gliomas. Radiolocalization was determined following intravenous (i.v.) or intracarotid (i.c.) injection with or without hyperosmotic mannitol induced disruption of the blood–brain barrier (BBB-D). As determined by γ-scintillation counting, 4 h after i.c. injection of 99mTc-EGF, 0.34% of the injected dose per gram (% ID/g) was localized in C6EGFR tumors, which expressed 105–106 EGFR sites per cell, compared to 0.07% ID/g in animals bearing C6 wildtype gliomas, which do not express EGFR. The corresponding tumor to brain ratios were 5.6 and 1.6, respectively. Tumors could be visualized by external γ-scintigraphy in rats bearing C6EGFR but not C6 wildtype gliomas, thereby establishing that radiolocalization was dependent upon receptor expression. Intracarotid administration of 99mTc-EGF significantly increased tumor uptake compared to i.v. injection (0.34 vs 0.14% ID/g, p<0.04). BBB-D disruption, followed by i.c. injection of 99mTc-EGF, however, did not significantly enhance tumor uptake compared to i.c. injection without BBB-D (0.45% vs 0.34% ID/g, p>0.1). The uptake of 99mTc-EGF was ∼4–9% ID/g in the liver and 12–20% ID/g in the kidneys after i.c. or i.v. administration. External γ-scintigraphy of regions of interest over the liver and kidneys revealed that ∼70–80% of the whole body radioactivity accumulated in these organs, and only 0.47–0.83% in the tumor following i.v. or i.c. administration of 99mTc-EGF. Our study has demonstrated that EGF can be used as a specific targeting agent for EGFR (+) rat brain tumors. However, it is unlikely that systemic injection of EGF-based bioconjugates can deliver sufficient amounts of the ligand to brain tumors for therapeutic purposes and direct delivery by means of either intratumoral injection or a variant of it such as convection enhanced delivery will be required.

Ultrasonography of urinary bladder disorders.

Ultrasonography is often recommended as the first diagnostic imaging modality in patients with hematuria or dysuria. It can provide information relative to the capacity of the urinary bladder, changes in bladder outline, changes in wall thickness, identification of mural and luminal masses, and identification of extrinsic lesions that may displace the bladder wall causing changes in its shape. Ultrasonography allows an evaluation of the entire urinary tract (except distal urethra) in both female and male dogs as well as the sublumbar region for lymphadenopathy.

Transvenous coil embolization of an extrahepatic portosystemic shunt in a dog: a naturally occurring model of portosystemic malformations in humans.

Abstract Congenital patent ductus venosus (PDV) occurs far more commonly in dogs than in people; consequently, the natural course of the disease in dogs was studied as a model to understand the pathophysiology behind the vascular anomaly and its response to therapy better. In this report, the authors describe the results of percutaneous coil embolization as a single procedure in a dog with a single congenital extrahepatic portocaval shunt and compare portosystemic vascular anomalies (PSVA) seen in dogs with those seen in children.

Biodistribution of Technetium-99m Labeled Epidermal Growth Factor Following Intracarotid Injection into Rats Bearing Intracerebral EGF Receptor (+) Gliomas

The gene for epidermal growth factor receptor (EGFR) and its cell surface membrane expression is amplified in a majority of high grade gliomas,1 suggesting that this receptor potentially may be a useful target for the selective delivery of 10B to EGFR (+) brain tumors.2 There has been increasing interest in the possible use of the EGFR as a molecular target for the delivery of boron compounds to EGFR (+) brain tumors for BNCT.3 Two requirements must be fulfilled. The first, as recently described by us,4 is the development of methodology to chemically construct boron-containing EGF bio-conjugates that retain their in vitro and in vivo affinity for the EGFR and the second is the ability to selectively deliver sufficient amounts of boronated EGF (B-EGF) to the tumor.5 Since exogenous EGF has a high propensity to localize in the liver and small amounts localize in the tumor following intravenous (i.v.) injection, optimization of delivery is critical to the successful use of B-EGF bioconjugates as targeting agents for brain tumors.6