Bombesin-like peptides are neurotransmitters and cancer growth factors. Several tumors, breast cancer among them, show one or more than one of the three known bombesin receptors. We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN). Labeling yield was 83 +/- 4%. Prone Scintimammography was performed on five patients affected by breast cancers (T categorization: two T1b and three T1c), after injecting 0.7 mg, 185 to 296 MBq (5 to 8 mCi) of the peptide. Total body scan did not show free technetium biodistribution. No adverse reaction was observed. Prone Scintimammography with 99mTc Sestamibi (99mTc SM) was also performed few days later. 99mTc BN detected all 5 cancers, whereas 99mTc SM only four: all the T1c and one T1b cancer. Two of them showed axillary node invasion that was detected by both the radiotracers. A fibroadenoma present on contralateral breast to the one with cancer, was not detected neither by 99mTc SM nor by 99mTc BN. Tumor/breast normal tissue ratio (T/B) was constantly higher with 99mTc BN than with 99mTc SM. Maximal T/B was measured as 1.79 with 99mTc SM and 2.25 with 99mTc BN 5 min after fast i.v. administration. In conclusion our 99mTc BN is taken up by primary breast cancer showing higher T/B than 99mTc SM (p < 0.01). In our limited scale, 99mTc BN appears to be safe and, in our limited scale, even more accurate than 99mTc SM for detecting breast cancer.
Aims and Background 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 amphibian 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. Methods and Study Design 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 this 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. Results 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 never 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. Conclusions 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.
Our first impression is that 99mTc BN is a useful breast cancer seeking agent and very promising for lymph node staging.
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