Nuclear medicine imaging of lung cancer and esophagus cancer

Background: Somatostatin receptors (SSTRs) occur in cancer tissue, and 99mTc-depreotide is a labelled somatostatin receptor analogue, binding to SSTRs subtype 2, 3, and 5.

Purpose: The general aim of the present thesis was to study somatostatin receptor scintigraphy (SSTRS) with 99mTc-depreotide in the diagnosis and characterization of cancers in the lung and oesophagus.

Study I evaluated the diagnostic value of the SSTRS with 99mTc-depreotide in 99 patients with suspected lung cancer. The sensitivity to detect malignancy was 94%, and to detect lung cancer 98%. The specificity was calculated on two sets of data. When all cases are used, the specificity was 52%. If the 12 pneumonias are excluded, the specificity was 77%.

Study II was performed on 19 patients with histologically proven non-small-cell lung cancer (NSCLC), where the expression of SSTR subtype 2 was looked for and found by immunochemical methods. The quantitative evaluation of 99mTc-depreotide was performed using region-of-interest analysis and includes tumour counts/cm3, background counts/cm3, and the ratio between tumour and background counts. SSTR subtype 2 expression was positively correlated to the degree of the tumour’s differentiation (p < 0.05). 99mTc-depreotide uptake in tumour cells did not correlate with tumour grade or SSTR subtype 2, MIB-1, or p53 expression.

Study III showed the feasibility of imaging oesophageal carcinoma with SSTRS with 99mTc- depreotide and optimal time intervals for imaging. None of the 13 cancer-free Barrett’s oesophagus patients in this study showed an increased 99mTc-depreotide uptake.

Study IV investigated the expression of SSTRs of subtype 2A, 2B, 3, and 5 in 28 patients with suspected oesophageal cancer, where expression was detected in small amount in adenocarcinoma and was absent in squamous cell carcinoma. There was no correlation between the 99mTc-depreotide uptake and the amount of SSTRs, and no correlation between the amount of SSTRs and the differentiation grade of the tumour.

Conclusion: SSTRS with the labeled somatostatin receptor analogue 99mTc-depreotide has a very high sensitivity for detecting lung cancer. A negative scintigraphy strongly suggests a benign lesion, and the method is useful in decision making with respect to surgery. There is an expression of SSTRS subtype 2 in NSCLC with a positive correlation between tumour differentiation and presence of SSTR subtype 2. There is no correlation between 99mTc-depreotide uptake compared to tumour differentiation, presence of SSTR subtype 2, p53, or MIB-1, and SSTRS cannot be used as a prognostic factor in patients with lung cancer.

SSTRS with 99mTc-depreotide of oesophageal cancer is feasible, but not suitable, for either screening or primary diagnosis, because of the method’s modest sensitivity. However, this method has a high specificity. The majority of patients with adenocancer of the oesophagus have a low amount of SSTRs, while most of the patients with squamous cell cancer do not have any of SSTRs.

List of scientific papers

I. Role of scintigraphy with Technetium-99m depreotide in diagnosis and management of patients with suspected lung cancer. Axelsson R, Herlin G, Bååth M, Aspelin P, Kölbeck K-G. Acta Radiol. 2008;49:295-302.
https://doi.org/10.1080/02841850701793777

II. Quantitative assessment of 99mTc-depreotide uptake in patients with non-small-cell lung cancer: immunihistochemical correlations. Herlin G, Kölbeck K-G, Menzel PL, Svensson L, Aspelin P, Capitano A, Axelsson R. Acta Radiol. 2009;50:902-8.
https://doi.org/10.1080/02841850903127477

III. Feasibility of imaging esophageal cancer with labeled somatostatin analogue. Herlin G, Ideström L, Lundell L, Aspelin P, Axelsson R. Int J Mol Imaging. 2011:279345.
https://doi.org/10.1155/2011/279345

IV. Quantitative assesment of 99mTc-depreotide uptake in esophageal cancer and precursor conditions and its reflection in immunohistochemically detected somatostatin receptors. Herlin G, Lundell L, Öst Å, Aspelin P, Svensson L, Axelsson R. [Manuscript]