Technetium Labeled Bombesin-like Peptide: Preliminary Report on Breast Cancer Uptake in Patients

Abstract

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.

Molecular Imaging of Breast Cancer Tissue via Site-Directed Radiopharmaceuticals

“…While low physiological uptake of 99m Tc-RP527 was observed in normal breast tissue, it did not affect the visualization of either the primary tumor or metastatic sites, which were successfully imaged in 4 out of 6 patients with tumor-to-background ratios of 1.7 to 3.4 and 2.6 to 7.2 at 1 and 6 hours p.i., respectively. Similar results were obtained by Scopinaro et al in a 2002 trial which compared the diagnostic capacity of a 99m Tc-labeled BBN analog with that of 99m Tc-sestamibi in five patients with infiltrating ductal carcinoma (Scopinaro et al, 2002). Although the identification of metastatic sites was achieved with both agents, detection of the primary tumor was higher for 99m Tc-BBN (100%) than for 99m Tc-sestamibi (80%).…”

“…Although the identification of metastatic sites was achieved with both agents, detection of the primary tumor was higher for 99m Tc-BBN (100%) than for 99m Tc-sestamibi (80%). This may be related to the higher affinity of BBN analogs for malignant breast tissue which often over-express the GRPr, allowing for improved tumor-to-background ratios when compared with 99m Tcsestamibi (1.4-2.3 vs. 1.0-1.8 at 5 minutes) (Scopinaro et al, 2002). While the results of these trials indicate that the detection/diagnosis of both primary breast cancer and metastatic sites can be achieved using radiolabeled BBN derivatives, the disadvantages demonstrated by these agents (moderate tumor-to-background ratios, hepatobiliary excretion) need to be addressed in order to recognize their full potential.…”

Targeted cytotoxic bombesin analog AN-215 effectively inhibits experimental human breast cancers with a low induction of multi-drug resistance proteins

“…Scintigraphy with radiolabeled bombesin/GRP analogs targeting BN/GRP receptors was successfully used for the detection of primary breast cancers and their lymph node metastases in several clinical studies (Van de Wiele et al 2000, Scopinaro et al 2002, Soluri et al 2003. For the targeted chemotherapy of BN/GRP receptor-positive cancers, we developed a cytotoxic hybrid of a bombesin analog linked to 2-pyrrolino-DOX.…”

“…In addition, the lymph node metastases from GRPRpositive tumors were all found to be GRPR positive, whereas in surrounding lymphoreticular tissue no receptor expression could be found (Gugger & Reubi 1999). In several clinical studies, primary breast cancers and their lymph node metastases were successfully detected using GRPR scintigraphy (Van de Wiele et al 2000, Scopinaro et al 2002, Soluri et al 2003. Therefore, GRPR scintigraphy could be used to select patients who may respond to therapy targeted to BN/GRP receptors.…”

Exploring new frontiers in molecular imaging: Emergence of68Ga PET/CT

“…In addition to the above examples, radiolabeled bombesin analogues have shown promise in several other tumors such as breast [80] and colorectal cancers [81] , using 99m Tc as the radioisotope. Use of the 68 Ga PET tracer is being studied, and publications can be expected in the near future.…”