| Part one The value of 11C-choline PET/CT imaging on prostate cancer and correlation with tissue markers of AR, PTEN, Ki 67Objective To investigate the potential of 11C-choline PET/CT imaging for diagnosis and staging of prostate cancer and detection of recurrent ones. To study the correlation between 11C-choline PET/CT imaging and the tissue markers, including AR, PTEN and ki67. The application of 11C-choline PET/CT imaging on lung caner and the real metabolic mechanism of 11C-choline in vivo were also investigated.Methods A total of 59 patients with prostate lesions were divided into two groups①49 cases without any therapy, male, age 47-92, PSA 1.1 ng/ml-100 ng/ml.②10 patients who have accepted either radical prostatectomy or maximum androgen blockade therapy. They all underwent 11C-choline PET/CT imaging before transrectal needle biopsy. PET/CT imaging were performed 5min after injection of 7.4 MBq/kg 11C-choline in supine position over 2 bed positions (3 min per position), covering the pelvis, and the whole body (6 bed) when necessary. After correction for measured attenuation, decay and scatter and iterative reconstruction, PET data were analyzed semi quantitatively by measuring maximum standardized uptake values (SUVmax) of the prostate lesions (target) and the muscles (non-target) and calculating their ratios (P/M). Visual analysis was performed using transverse, sagittal and coronal slices as well as three-dimension images. The results of 11C-choline PET/CT were compared to pathologic results which were acquired by radical prostatectomy or biopsies specimens. Sensitivity, specificity, positive and negative predictive value of PET/CT in diagnosis on prostate cancer were calculated and all statistical analysis were made by SPSS 13.0.Results①21 prostate caner and 28 benign prostate hyperplasia (and/or chronic prostatitis) were proven histologically. All PCa could be visualized as avid accumulation in the gland. Among 28 benign diseases, high uptake of the radioactivity was noticed in 23 BPH while 5 BPH showed little accumulation of C-11 choline. With PET/CT precise localization, a diffuse accumulation of radioactivity in the entire prostate gland was observed in 15 and a solitary hot spot within the peripheral zone of prostate gland was visualized in 6 patients among 21 PCa cases.27 of 28 BPH patients could be seen symmetrical uptake of C-11 choline within the central zone of prostate.②The mean values of SUVmax of PCa and BPH were 7.87±5.74 and 4.95±5.14, respectively. There was no significant difference between these two groups. (t=2.02, p>0.05). The mean P/M of PCa and BPH were 4.21±1.61 and 1.87±0.98, respectively. The statistical differences of P/M between them were significant (t=2.04, p<0.01).③Using 2.3 (P/M) as criterion, C-11 choline PET/CT imaging showed sensitivity of 90.48%, specificity of 85.71% and negative predictive value of 92.31%. The precise localization of the radioactivity hot spot in different part of the prostate could help the diagnosis a lot which is the advantage of PET/CT.④6 patients with focal uptake in lymph node and/or bone metestases were detected by 11C-choline PET/CT which demonstate it is useful in staging of prostate cancer.⑤Among 4 patients who underwent radical prostatectomy 1 patient was found that his postate cancer was still existed. And 2 patients were detected with recurrent tumor in 6 cases which accepted maximum androgen blockade therapy.⑥A significant positive association was found between 11C-choline accumulation and Ki67 (rs=0.764, P<0.01; rs=0.660, P<0.01) respectively in all the 49 patients and prostate cancer patients.Conclusion 11C-choline PET/CT is a valuable non-invasive imaging technology in the diagnosis, staging and detection of recurrent of prostate cancer. The parameter P/M could differentiate prostate cancer from benign lesions better than SUV. A significant positive association was found between 11C-choline accumulation and Ki67 in prostate cancer patients.Part two The research of 11C-choline PET/CT imaging and choline metabolism on lung cancerObjective To investigate the potential of 11C-choline PET/CT imaging for diagnosis and staging of lung cancer in order to find a more accurate tracer than 18F-FDG in early diagnosise of cancer. To study the proportion of phosphorylation pathway and acetylation pathway of choline in different types of lung cancer in order to investigate the real metabolic mechanism of 11C-choline in vivo.Methods 38 patients with suspicious lung cancer who were examined with 11C-choline PET/CT imaging had finally had lung surgery in 32 while the other 6 patients were found to have distance metastasis. Lung cancer sample and normal lung tissues were saved in 18 patients for further choline metabolism research. Without fasting, patients were injected of 7.4MBq/kg of 11C-choline intravenously five minutes before imaging. PET images were acquired in supine position over 2 bed positions (3 min per positron) from the upper neck to the lower edge of liver and whole body(6 bed positions) when necessary. The parameters of the multidetector helical CT scan were 140 kV,80 mA,0.8 s per tube rotation, slice thickness of 5 mm, pitch of 6, and table speed of 11.25 mm/s. PET images were reconstructed with the iterative reconstruction ordered-subset expectation maximization likelihood algorithm of the manufacturer after attenuation correction based on the CT dataset. Consecutive transverse PET/CT slices of 4.25 mm thickness were generated. Lung cancers were analysed visually and semiquantitatively using the ratio of tumour-to-normal radioactivity (T/N ratio) and standardized uptake value (SUV). Mediastinal lymph node metastases were analysed visually. RT-PCR and Western blot were used to investigate the expression of choline acetyltransferase (ChAT) and choline kinase (ChoK) genes in lung cancer specimens and the normal lung tissues.Results①All lung cancer could be visualized as avid accumulation in the lesions. But the three benign diseases, including two tuberculosis and one inflammatory pseudotumor also showed high uptake of the radioactivity. It is hard to differentiate malignant from benign lesions in 11C-choline PET/CT imaging.②The mean values of SUVmax of lung cancer and benign lesions were 4.82±1.79 and 6.95±1.1, respectively. There was no significant difference between these two groups. (t=3.18, p>0.05). The mean T/NT of malignant and benign lesions were 5.59±2.19 and 8.07±1.75, respectively.. The statistical differences of T/NT between them were still not significant (t=3.18, p>0.05).③The SUVmax and T/NT of the all 14 squamous cell carcinoma patients were 4.98±1.96 and 6.0612.01 respectively, while the SUVmax and the T/NT of the 10 adenocarcinoma patients were 4.09±1.62 and 4.68±2.05. The difference was not statistically significant between the squamous cell carcinoma and adenocarcinoma.④6 patients with distant metestases were detected by 11C-cholinePET/CT which demonstate it is useful in staging of lung cancer. In the assessment of mediastinal lymph node involvement, 11C-choline PET/CT detected 10 patients in all 13 patients proven by pathology. The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 11C-Choline PET/CT in the detection of lymph node metastasis is 67.6%,84.2%,80.6%,72.7%,72.7%.⑤The expression of ChAT mRNA and protein were enhanced in 9 of 18 lung tumor specimens; and the expression of ChoK mRNA and protein were increased in 14 of 18 lung tumor specimens comparing with the normal lung tissues.8 of 18 lung cancer specimens were obvious increased both in the expression of ChoK and ChAT.Conclusion In this study, all lung cancer could be visualized as avid accumulation in the lesions while the benign diseases, including tuberculosis and inflammatory pseudotumor could also show high uptake of the radioactivity. No matter SUVmax or T/NT, there was no significant difference between the malignant and bening groups. It is difficult to differentiate malignant from benign lesions in 11C-choline PET/CT imaging. The difference was not statistically significant between the squamous cell carcinoma and adenocarcinoma in SUV and T/NT. Both phosphorylation pathway and acetylation pathway of choline were existed in different types of lung cancer.
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