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J Nucl Med. 2008; 49 (Supplement 1):48P
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Radiopharmaceutical Chemistry: Dosimetry/Radiobiology

Clinical Dosimetry

Radiotherapy of 4T1 tumors with Lu-177-DOTA-PEG-scVEGF

Francis Blankenberg1, Zoia Levashova1, Marina Backer2 and Joseph Backer2

1 Radiology, Stanford University, Stanford, California; 2 Sibtech, Inc., Brookfield, Connecticut

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Objectives: Single chain (sc)VEGF is a truncated monomeric form of VEGF121 with a unique cysteine residue for site-specific attachment of therapeutic and imaging moieties. Using Cy5.5-scVEGF we have defined an "angiogenic rim" of uptake that consistently extended beyond BLI defined margins of 4T1luc mammary adenocarcinomas. We now wish to leverage the high uptake of the angiogenic rim to kill tumor vessels and tumor cells (via bystander effect) with Lu-177-DOTA-PEG-scVEGF(Lu-scVEGF).

Methods: 1mCi, (1200 rads to tumor center) or 3.8 mCi (5000 rads to tumor center) of Lu-scVEGF (40 to 60µCi/µg) was injected via tail vein in 4T1luc tumor bearing mice 12 days after implantation of 50,000 cells into the left axillary mammary fat pad. Mice were then sacrificed at 6 to 7 days after injection along with untreated controls.

Results: Animals tolerated each dose without signs of distress, weight loss, or lethargy. There was a significant reduction in tumor growth at both doses (Table I) compared to control. There was also a 40% decrease (p = 0.016) in the number of stained vessels in the Lu-scVEGF treated as opposed to untreated 4T1 tumor as seen by antibody to VEGFR-2. Biodistribution assay in another set of tumor mice (n=5 per group) revealed that Lu-scVEGF was retained in tumor at 4hr, 24hr, 4 and 6 days (2.32 ± 0.37, 1.55 ± 0.18, 0.76 ± 0.13, 0.55 ± 0.10 %ID/g, respectively.) with a 4-5 ratio of tumor rim to muscle uptake at all time points.

Conclusions: It is possible to leverage the angiogenic rim of tumors to deliver therapeutic doses of Lu-scVEGF.

Research Support: 1 R43 EB006679-01A2 (to JB and FG)


Figure 1





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Right arrow Articles by Backer, J.