PT  - JOURNAL ARTICLE
AU  - Ankit Watts
AU  - Baljinder Singh
AU  - Ninjit Dhanota
AU  - Mehak Vohra
AU  - Rajender Kumar
AU  - Harmandeep Singh
AU  - Amanjit Bal
AU  - Rakesh Kapoor
AU  - Sunil Arora
AU  - Hans Wester
AU  - Bishan Radotra
AU  - Bhagwant Mittal
AU  - Digambar Behera
TI  - In vivo imaging and quantification of CXCR4 expression in lung cancer subtypes using <sup>68</sup>Ga-Pentixafor PET/CT and Flow cytometry analysis: A single center and First Asian Experience
DP  - 2019 May 01
TA  - Journal of Nuclear Medicine
PG  - 84--84
VI  - 60
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/60/supplement_1/84.short
4100  - http://jnm.snmjournals.org/content/60/supplement_1/84.full
SO  - J Nucl Med2019 May 01; 60
AB  - 84Objectives: To evaluate the diagnostic performance of 68Ga-Pentixafor PET/CT for imaging CXCR4 expression in lung carcinoma and to validate the specificity of the tumor uptake of the radio-tracer with the CXCR4 receptor density in different tumor subtypes. Methods: Eighty-Six patients (72M: 14F; mean age= 60± 10 yrs) with clinical/radiological suspicion of lung carcinoma were included in the present study. Bronchoscopy (n=53) and PET/CT guided automated robotic arm assisted (ARA) guided (n=33) biopsied lung tissue samples were subjected to fluorescence-activated cell sorting (FACS) and histo-pathological analysis. Quantitative FACS analysis was done using CD184 antibody to document Mean Fluorescence Index (MFI) (in-vivo measure of CXCR4 receptor density). While lung cancer subtypes were documented from histopathological analysis.68Ga-Pentixafor PET/CT was performed in all these patients. About 110-150 MBq radioactivity of freshly prepared 68Ga-Pentixafor (synthesised by using Scintomics (Germany) automated chemistry module procured under DST-FIST Project Funding) was administered intravenously. Whole body contrast enhanced CT (120Kv, 200-300mAs, Pitch 0.98:1, Slice thickness 3.75mm) followed by PET from skull to proximal thighs (3min/bed position; 7-8 positions) was acquired at 1-hour post injection. Data was reconstructed using iterative method (3 iterations, 28 sub-sets). SUVmax values of the primary lung tumors were documented. Results: 59/86 patients were found to be of Non-Small Cell (NSCLC) variant while 11/86 patients were of small cell lung carcinoma (SCLC) , a small subset of patient (5/86) had primary lung neuroendocrine (NET) tumor while 1/86 showed signs of metastatic lung component upon histo-pathological analysis. Ten patients were found to be of non-malignant pathologies. Mean 68Ga-Pentixafor SUVmaxvalue in squamous cell and adenocarcinoma patients was 5.6±1.6 (n=44) & 7.3±1.7 (n=11), respectively. The corresponding MFI value assessed in these patients was 127±58 and 153±50, respectively. While 4 patients were found to be of NSCLC 'not otherwise specified' (NOS) with mean SUVmax value of 5.7±1.4. On the other hand, in SCLC patients (n=11), the mean SUVmax value was 9.1±2.0 with MFI score of 167±56. In patients with primary lung NET disease (n=5), the mean SUVmax value was 5.1±1.1 with MFI score of 96 ± 22. Lowest mean SUVmax values (4.5±1.3) were found in non-malignant pathologies with complementing low MFI score of 82±37. This study demonstrates that 68Ga-Pentixafor uptake is through specific targeting of CXCR4 expression and varies as a function of CXCR4 receptor density in different lung cancer variants. The uptake and CXCR4 expression being highest in SCLC followed by adenocarcinoma and squamous cell carcinoma (NSCLC) and lung NETs respectively.Fig 1- 68Ga-Pentixafor PET/CT (Whole Body MIP & Axial slice of the primary lung tumor) images showing differential expression of CXCR4 receptors in different sub-types of lung carcinoma. Conclusions: This study concludes that 68Ga Pentixafor is a promising future PET molecule for imaging CXCR4 over expression reported in lung cancer and many other human malignancies. This novel PET tracer has the potential of becoming a powerful tool for monitoring therapy response to CXCR4 inhibitors and also for the development of emerging alpha/beta targeted therapies in advanced stage lung carcinoma. $$graphic_078CAB3A-2C78-49E0-8A2E-0F11F0BF0518$$