Radiation Dosimetry for CXCR4 chemokine receptor targeting probe-⁶⁸Ga-Pentixafor in patients with Lung Carcinoma: An approach to future theranostics

Objectives: To quantify the biokinetics by computing- whole body effective dose and absorbed doses to various organs as well as to the lung lesions from ⁶⁸Ga-Pentixafor PET/CT in lung carcinoma patients.

Methods: A total of nine patients (8 M: 1F ; mean age = 57.9 ± 11.2 yrs.) with histopathological confirmed lung carcinoma (4- NSCLC-squamous cell, 1- NSCLC-adenocarcinoma, 3- SCLC and 1 of sarcomatoid lung carcinoma) were included in the study. All the patients underwent five point serial PET/CT imaging - rapid dynamic 3 multiple-bed positions of 300 sec and subsequent 4 static whole body encompassing 6-9 bed positions (3min/frame) acquired at 30 min, 1 h, 2 h, and 3 h after administration of the radiopharmaceutical. All the imaging sessions were performed on Time of flight (TOF) based PET/CT scanner (Discovery 710, GE Healthcare, USA). Low dose CT scans for attenuation correction were acquired (40mAs, 120 keV, 3.75-mm slice thickness, rotation time 0.5sec, pitch 0.98:1, matrix 512x512) for set of images. PET data after iterative reconstruction was fused with CT images and pushed to HERMES hybrid dosimetry (v 2.4) workstation for processing. Volume of interest (VOI’s) were drawn on various body organs and lung lesions on one serial PET image and was replicated on the subsequent serial image data. Time activity curves (TAC) were obtained for the organs of interest by applying curve fitting and integration to obtain the cumulated activity and residence time. The data was then analysed on OLINDA dosimetry (v 2.1.1) software to compute absorbed doses and whole body effective doses for the standard 70-kg adult male model with OLINDA/EXM.

Results: Highest absorbed dose was seen in the urinary bladder (13.2E-02 mGy/MBq) followed by spleen (6.7E-02 mGy/MBq), kidneys (4.7E-02 mGy/MBq), and red marrow (2.7E-02 mGy/MBq). The absorbed doses standardized to 150MBq of the injected activity of ⁶⁸Ga-Pentixafor were found to be 19.7, 10.0, 7.1, 4.1 mGy for urinary bladder, spleen, kidneys and red marrow respectively. The various other organs showed a minimal absorbed dose. The absorbed doses to the lung lesions ranged from 6.3E-03 to 9.7E-02 mGy/MBq. The highest absorbed dose to the lung mass was seen in patients with SCLC (5.9E-02 mGy/MBq) followed by NSCLC-adenocarcinoma (3.0E-02 mGy/MBq) and NSCLC-squamous cell (1.7E-02 mGy/MBq) correlating with the differing CXCR4 expression in these variants of lung carcinoma. The whole-body effective dose was estimated to be 2.43±0.64 mSv (normalized for 150.0MBq activity of the administered dose of ⁶⁸Ga-Pentixafor). The same is about 1/3rd of the dose that the patients typically receive from a conventional (10.0mCi/370MBq) ¹⁸F-FDG-PET scan.

Conclusions: ⁶⁸Ga-Pentixafor showed favourable pharmacokinetics and organs’ radiation absorbed and whole-body effective doses, thus was documented as safe for human administration. The variability in the ⁶⁸Ga-Pentixafor uptake in different lung cancer variants was tied with CXCR4 receptor expression. Therefore, the PET quantification of ⁶⁸Ga-Pentixafor uptake in lung cancer may be considered as in-vivo CXCR4 expression disease mapping and can be used for titration of the doses of futuristic CXCR4 based radio (alpha/beta) theranostics. This approach could be of significant interest in small cell lung carcinoma which is known to have high CXCR4 over-expression and we have documented higher absorbed dose to the lung mass than all other lung cancer variants. The favourable dosimetric results (higher target to non-target absorbed doses) also paves way for future radio-theranostic in various solid tumors and haematological malignancies as CXCR4 receptors are overexpressed in more than 30 human malignancies.

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