PET Using a GRPR Antagonist 68Ga-RM26 in Healthy Volunteers and Prostate Cancer Patients

Abstract

This study was designed to analyze the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist PET tracer, ⁶⁸Ga-RM26; to assess its clinical diagnostic value in prostate cancer patients; and to perform a direct comparison between GRPR antagonist ⁶⁸Ga-RM26 and agonist ⁶⁸Ga-BBN. Methods: Five healthy volunteers were enrolled to validate the safety of ⁶⁸Ga-RM26 and calculate dosimetry. A total of 28 patients with prostate cancer (17 newly diagnosed and 11 posttherapy) were recruited and provided written informed consent. All the cancer patients underwent PET/CT at 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of ⁶⁸Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 posttherapy) underwent ⁶⁸Ga-BBN PET/CT for comparison within 1 wk. ^99mTc-MDP (methylene diphosphonate) bone scans were obtained within 2 wk for comparison. GRPR immunohistochemical staining of tumor samples was performed. Results: The administration of ⁶⁸Ga-M26 was well tolerated by all subjects, with no adverse symptoms being noticed or reported during the procedure and at 2-wk follow-up. The total effective dose equivalent and effective dose were 0.0912 ± 0.0140 and 0.0657 ± 0.0124 mSv/MBq, respectively. In the 17 patients with newly diagnosed prostate cancer, ⁶⁸Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with an SUV_max of 6.49 ± 2.37. In the 11 patients who underwent prostatectomy or brachytherapy with or without androgen deprivation therapy, ⁶⁸Ga-RM26 PET/CT detected 8 metastatic lymph nodes in 3 patients with an SUV_max of 4.28 ± 1.25 and 21 bone lesions in 8 patients with an SUV_max of 3.90 ± 3.07. Compared with ⁶⁸Ga-RM26 PET/CT, GRPR agonist ⁶⁸Ga-BBN PET/CT detected fewer primary lesions and lymph node metastases as well as demonstrated lower tracer accumulation. There was a significant positive correlation between SUV derived from ⁶⁸Ga-RM26 PET and the expression level of GRPR (P < 0.001). Conclusion: This study indicates the safety and significant efficiency of GRPR antagonist ⁶⁸Ga-RM26. ⁶⁸Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis. ⁶⁸Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer.

Keywords: GRPR antagonist; PET; RM26; dosimetry; prostate cancer.

FIGURE 1.

(A) Representative torso maximum-intensity-projection images of a 42-y-old female healthy volunteer at 5, 15, 30, 45, and 60 min after intravenous injection of ⁶⁸Ga-RM26. Main regions with prominent ⁶⁸Ga-RM26 uptake are pancreas, kidneys, urinary ducts, and bladder. (B) PET/CT showed tracer uptake in major organs at 30 min after intravenous administration of 129.5 MBq (3.5 mCi) of ⁶⁸Ga-RM26 to a 48-y-old male healthy volunteer.

FIGURE 2.

(A) Different levels of ⁶⁸Ga-RM26 accumulation in newly diagnosed prostate cancer and immunohistologic staining against GRPR of the biopsy samples. (B) Correlation of PET quantification and GRPR expression score in primary prostate cancer and metastases.

FIGURE 3.

⁶⁸Ga-RM26 PET/CT (A) and ^99mTc-MDP bone scintigraphy (B) in a 62-y-old man with recurrent prostate cancer, who was diagnosed as having prostate cancer 4.5 y earlier and underwent radiotherapy and androgen deprivation therapy. Current PSA value was 36.0 ng/mL. ⁶⁸Ga-RM26 PET/CT detected bone metastasis lesion in right ilium and surrounding soft tissues.

FIGURE 4.

Comparison of ^99mTc-MDP bone scintigraphy (A), ⁶⁸Ga-RM26 PET/CT (B), and ⁶⁸Ga-BBN PET/CT (C) in a 73-y-old man diagnosed as having prostate cancer (white arrow) with lymph node involvement (red arrow) and bone metastasis (yellow arrow) before prostatectomy. ⁶⁸Ga-RM26 PET/CT detected primary tumors, multiple lymph node involvement, and bone metastasis lesion, whereas those lesions did not significantly show up on ^99mTc-MDP bone scintigraphy and showed extremely mild uptake on ⁶⁸Ga-BBN PET/CT.

FIGURE 5.

Quantitative comparison between ⁶⁸Ga-RM26 PET/CT and ⁶⁸Ga-BBN PET/CT in primary tumor (A), lymph node metastases (B), and bone metastases (C) in 22 of 28 patients who underwent both ⁶⁸Ga-RM26 and ⁶⁸Ga-BBN PET/CT.