Position of Nuclear Medicine Modalities in the Diagnostic Workup of Cancer Patients: Lung Cancer – 2
DIFFERENTIATION OF LUNG MASSES WITH 99MTC DEPREOTIDE
The majority of malignant lung tumor cells Express receptors for somatostatin. Therefore, somatostatin receptor scintigraphy has been used for the detection and staging of lung cancer.99mTc depreotide, which binds to the somatostatin receptor subtypes 2, 3 and 5, has been used for the differentiation of indeterminate lung nodules. Blum et al. reported the results of a multicenter trial in 114 patients,revealing a sensitivity of 97% (85/88 malignant lesions found) and a specificity of 73% (19/26 benign lesions correctly classified), respectively. The radiopharmaceutical is approved for the use in lung nodules with high probability of malignancy in Europe and the United States. To our knowledge, comparative studies between 99mTc depreotide and FDG-PET have not been published in peer reviewed journals. The use of 99mTc depreotide can be recommended for institutions without access to FDG-PET and in cases with increased risk at surgery. With a negative predictive value of 86% (19/22), the probability of missing a potentially curable lung cancer is 14%. This risk must be compared to the individual chance of a fatal complication during surgery.
The detection of metastatic bone disease by skeletal scintigraphy is a classical application of nuclear medicine in cancer patients. Osteoblastic activity isinduced by the majority of bone metastases and it can be visualized by osteotropic tracers with a higher sensitivity than conventional radiographic imaging which requires a minimum size of 1 cm and a focal increase of 30% or a loss of at least 50% of the bone mineral to detect sclerotic or lytic lesions, respectively. 99mTc-labeled phosphonates are the preferred tracers for bone scintigraphy which is indicated in patients with bone pain, elevated serum calcium or elevated alkaline phosphatase levels.2, 3 The sensitivity for the detection of bone metastases is at least 90%, but the specificity ranges only between 40% and 90%.8 If the bone scan is positive, frequently further examinations are necessary. The high negative predictive value of 90% is sufficient, however, to exclude bone metastases. Skeletal scintigraphy has the potential to detect an osseous infiltration as well as bone metastases.
ESTIMATION OF POSTOPERATIVE LUNG FUNCTION
Quantitative lung perfusion scintigraphy is a Standard procedure for the estimation of the loss in function after lung resection (functional resectability) or irradiation.The residual lung volume is predicted as a relative value from the percentage loss of the relative radioactivity in the lung segments (or lobes) intended for resection or irradiation.
PREDICTION OF RESPONSE TO CHEMOTHERAPY
Chemotherapy plays an important role in advanced or unresectable lung cancer.In multidrug resistance of lung cancer, the P-glycoprotein (Pgp), encoded by the multidrug resistance gene MDR1, is a keyfactor.Pgp, an energy-dependent efflux pump, prevents the accumulation of some chemotherapeutic agents such as doxorubicine, paclitaxel, and the vinca-alkaloids and therefore reduces the response rate. Certain cationic lipophilic radiopharmaceuticals, such as 99mTc-ethoxyisobutylisonitrile (99mTc-MIBI), are also a substrate of Pgp so that the scintigraphic retention of 99mTc-MIBI can be used as a non-invasive imaging test for Pgp assessment. The ability of quantitative 99mTc MIBI scintigraphy to predict chemosensitivity has been under investigation in the last years. Ceriani et al.reported a sensitivity of 83% and a specificity of 84% in predicting the response to chemotherapy of lung cancer. Similar results were reproduced by other groups.For defining the final role of 99mTc MIBI SPECT in the management of lung cancer patients, further studies are needed; however, it is difficult to design such studies since there are no definite recommendations of cytostatic substances to be used in advanced lung cancer.
Positron emission tomography
The increased importance of FDG-PET in the workup of lung cancer patients is related to several propitious factors which justify its use in oncology, even if it is an expensive imaging modality.Today, the instrumentation is quite sophisticated resulting in high resolution images (6 mm or less in clinical applications). The imaging principle employs attenuation correction and compensation for scatter allowing quantitative measurements. The metabolic tracer, 2-F-18-fluoro-2- deoxy-D-glucose (F-18 FDG), a glucose analogue, is most frequently used because of the high glucose consumption of most lung tumors. However, increased glucose metabolism is not completely specific for a malignant lesion but is also detectable in acute inflammatory reactions and other benign conditions. Nevertheless, by metabolic characterization of tissues, FDG-PET has the ability to overcome several limitations of morphological imaging modalities like CT and MRI. FDG has been approved in Europe for the differential diagnosis of pulmonary nodules and masses, for the staging of non-small cell lung cancer, for the detection of metastases of lung cancer, and for the detection of recurrent lung cancer. This corresponds to the broad spectrum of indications for FDG-PET in lung cancer.
PET SCANNING TECHNIQUE
Performing whole-body PET with high diligence is very important for achieving a high diagnostic sensitivity (and specificity). Optimal patient preparation must be strictly followed (Table VII), as should be a sufficient waiting period 25, 26 before image acquisition due to FDG blood clearance, especially in the mediastinum and lung. Attenuation correction is necessary for the detection of small mediastinal lymph node metastases, as is iterative reconstruction when there is intense uptake in primary tumors or the myocardium, to avoid reconstruction artefacts and to detect lymph node metastases near the primary tumor. Semiquantitative measurement of the FDG uptake as standard uptake value (SUV) should be performed routinely in all or in the most relevant tumor lesions. Because PET images contain limited anatomical information, a chest CT should always be available for accurate localization. Optimal information is obtained by anatometabolic image fusion of PET (metabolism) and CT (anatomy). It can be foreseen that anatometabolic image fusion (obtained by software within a PACS or using PET/CT) will be incorporated as a routine method in lung cancer staging in the future. Whether gamma camera coincidence imaging will be able to achieve the high sensitivity obtained by dedicated PET scanners remains an open question. Early results show a markedly lower sensitivity for coincidence cameras (55% of that of “dedicated” PET).
Pulmonary tumor lesions were detected most successfully (13 out of 14, i.e. 93%), but only 65% of mediastinal lymph node metastases were diagnosed. Technological advancements such as attenuation correction will surely improve this technique in the future.28 Other PET radiopharmaceuticals such as positronlabeled proliferation markers like L-thymidine (FLTPET), antibodies (Immuno-PET), receptor ligands (Receptor-PET), amino acids (e.g., C-11 methionine or 2-O-fluoro-ethyl-tyrosine [FET-PET]) and other tracers have only been used in a small number of patients and do not play a role in routine clinical practice up to now.