Evaluation of biological response modifiers in the enhancement of tumor uptake of technetium-99m labeled macromolecules

A preliminary report

M.L. Thakur, J. DeFulvio, J. Tong. Elizabeth John, M.R. McDevitt and I. Damjanov

Radiation Oncology and Nuclear Medicine. Thomas Jefferson University Hospital. Department of Nuclear Medicine. 11th & Walnut Sts., Philadelphia. PA 19107. USA

Correspondence to: M.L. Thakur. Radiation Oncology and Nuclear Medicine. Thomas Jefferson University Hospital. Department of Nuclear Medicine, 11th & Walnut Sts.. Philadelphia. PA 19107. USA.

Imaging tumors with radioactive monoclonal antibodies remains attractive but continues to be challenging. With the hypothesis that the use of biological response modifiers (BRMs) may augment the tumor uptake, technetium-99m(^99mTc)-labeled tumor necrosis factor (TNF) and nuclear histone specific TNT-1-F(ab')₂ were evaluated in tumor bearing mice given a single dose of interferon (IFN), Ukrain or pokeweed mitogen as BRMs. As early as U h post injection (p.i.) of the radioactive macromolecules, the absolute tumor uptake (% administered dose/g) of each agent was enhanced (e.g., TNF. control = 1.8 ± 0.4, Ukrain = 3.2 ± 0.5, P = 0.006) and tumor to muscle ratios were elevated (e.g., TNF, control a 4.1 ± 2.2, interferon 8.3 ± 2.7, P=0.01). The absolute tumor uptake remained practically unchanged at 4 h p.i. Generally with BRMs, the blood clearance was rapid and tumor/blood ratios and tumor/muscle ratios were higher than in the control group, increasing to greater than 200% for IFN as a BRM.

The early enhancement in tumor uptake of macromolecules. leading to excellent 8delineation of tumors by scintigraphy is highly encouraging and warrants further studies to explore the full potential of BRMs.

Key words: Technetium-99m-labeled macromolecule: Biological response modifiers: Tumor uptake enhancement