Indium-111-octreotide Scintigraphy, Intraoperative Gamma-detector Localisation and Somatostatin Receptor Expression in Primary Human Breast Cancer

Abstract

12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood. Ratios between the 111In activity concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation detector was used intraoperatively for radioactivity measurements of the biopsies in situ and ex vivo. The sstr-subtype profiles were determined by northern blot analysis and the relative expression of sstr2 by ribonuclease protection assay (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast cancer tumours. The scintigraphic image showed no correlation with the histopathological type of the tumour or with the abundance of oestrogen/progesterone receptors on the tumour. Two patients with a massive tumour infiltration of the lymph nodes had a distinct positive SRS of the ipsilateral axilla. In one patient with three nodal metastases the scintigraphic image of the axilla was weak but visible. Four other patients with a negative axillary scintigraphy had 1-2 lymph node metastases. The Ti/B ratios for the breast tumours varied between four and 33 and were not different from Ti/Br ratios. In lymph node metastases the Ti/B ratios were higher (10-41). Intraoperative detector measurements showed a significant difference between the breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two patients with lymph node metastases exhibited a significantly increased uptake ex vivo by detector measurements, but in only one of them in situ. All tumour biopsies expressed the presence of sstrl, 3, 4 and 5, but not of sstr2 at northern analysis. On the other hand, sstr2 was detected in all tumours by RPA and immunocytochemistry. Preoperative SRS visualised primary breast cancer lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour infiltration. Intraoperative use of the scintillation detector could not exclude axillary metastases in situ. The low Ti/B values of both primary tumours and metastases indicate limitations of the radiopharmaceutical used.

Comparison of the Therapeutic Response to Treatment with a 177Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models

“…Cescato et al (6) compared binding of the SSTR antagonist 177 Lu-DOTA-BASS with the SSTR agonist 177 Lu-DOTA-octreotate and reported 11 6 4-fold-higher binding of the antagonist in 7 breast carcinomas analyzed by in vitro autoradiography. Furthermore, imaging studies in breast cancer patients using SSTR agonists have been performed with varying results (22,23). The use of JR11 may improve these results and provide imaging and therapy options for different tumors.…”

Clinical Relevance of Targeting the Gastrin-Releasing Peptide Receptor, Somatostatin Receptor 2, or Chemokine C-X-C Motif Receptor 4 in Breast Cancer for Imaging and Therapy

“…In the past decade, imaging of breast cancer patients using SSTR2 radioligands has been studied with varying results (10,11). Currently, considerably improved SSTR2-directed radiotracers and imaging equipment are available.…”

Evaluation of two intraoperative gamma detectors for assessment of 177Lu activity concentration in vivo

“…However, statistical analysis resulted in similar performance for both detectors for the tumour sizes and activity concentration ratios evaluated, probably due to the higher sensitivity of detector A. Results from clinical studies where intraoperative gamma detectors were used for radioguided surgery suggest that the lowest C T / C Bgr level needed to detect a tumour in surrounding normal tissue is around 1.2–1.5 [18, 21, 22, 43], but higher levels of up to 2 have been suggested as the ratio value corresponding to the lowest limit of detectability [44–47]; the reason for this difference is probably due to the sensitivity of the detector, the number of photons sampled and the biological uncertainties in radionuclide concentration in tissues. Both detectors evaluated in the present work could be used clinically, but the clinical application would decide which parameter is more important, and thus which detector would be best.…”