Phase I trial of technetium [Leu13] bombesin as cancer seeking agent: possible scintigraphic guide for surgery?

Bombesin-like neuropeptides work as neurotransmitters and growth factors at the same time. Several human cancers show overexpression of three receptors for mammalian counterparts of amphibia bombesins (ABNs), ie gastrin-releasing peptide (GRP), neuromedin B (NMB) and possibly another peptide. ABNs in turn are able to bind to mammalian and human receptors in vitro, and it is therefore interesting to study radioisotope-labeled bombesin (BN) and BN-like peptides as cancer seeking agents.

Starting from the amino acid sequence of [Leu13] ABN, the Demokritos Institute has synthesized and labeled with technetium a new BN-like peptide that has the same biological characteristics as the amphibian peptide; changes were made only in the N-terminal part of the tetradecapeptide. After having obtained satisfactory results with 99mTc BN in a preclinical study, we started a phase I trial involving cancer patients as well as normal volunteers in Tomsk. Three normal volunteers, one patient with small cell lung cancer and one patient with primary prostate cancer were studied after iv injection of 185 MBq, corresponding to 0.7 micrograms of 99mTc BN. Dynamic images of the tumors were acquired for 20 mins, followed by SPET. Total body images were acquired in patients and normal volunteers 1 and 3 h after 99mTc BN acquisition. In addition, 99mTc sestamibi scintigraphy was performed in the patient with small cell lung carcinoma.

No relevant side effects were observed. Both tumors were well visualized on early 1-2 mins images with planar as well as tomographic imaging. Total body images showed radioactivity in the liver, kidneys and thyroid gland. The stomach and spleen were ever imaged. Radioactivity was found in the urinary bladder 4 mins after injection in the patient with prostate cancer. Three-hour total body scans showed radioactivity in the duodenum. In the patient in whom also 99mTc sestamibi scintigraphy was performed, thyroid uptake was much higher with sestamibi than with 99mTc BN, whereas the uptake of small cell lung carcinoma was higher with 99mTc BN than with sestamibi.

99mTc BN is able to clearly image tumors with BN receptor overexpression. Our first impression is that in the future this radiopharmaceutical may serve as a cancer seeking agent and, due to its high tumoral uptake, also as a radiotracer for radioisotope-guided surgery.