[89Zr]Zr-PSMA-617 PET/CT in biochemical recurrence of prostate cancer: first clinical experience from a pilot study including biodistribution and dose estimates

Abstract

Purpose: Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become increasingly important in the management of prostate cancer, especially in localization of biochemical recurrence (BCR). PSMA-targeted PET/CT imaging with long-lived radionuclides as ⁸⁹Zr (T_1/2 = 78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our first clinical experience including preliminary biodistribution and dosimetry data of [⁸⁹Zr]Zr-PSMA-617 PET/CT in patients with BCR of prostate cancer.

Methods: Seven patients with BCR of prostate cancer who revealed no (n = 4) or undetermined (n = 3) findings on [⁶⁸Ga]Ga-PSMA-11 PET/CT imaging were referred to [⁸⁹Zr]Zr-PSMA-617 PET/CT. PET/CT imaging was performed 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of 111 ± 11 MBq [⁸⁹Zr]Zr-PSMA-617 (mean ± standard deviation). Normal organ distribution and dosimetry were determined. Lesions visually considered as suggestive of prostate cancer were quantitatively analyzed.

Results: Intense physiological uptake was observed in the salivary and lacrimal glands, liver, spleen, kidneys, intestine and urinary tract. The parotid gland received the highest absorbed dose (0.601 ± 0.185 mGy/MBq), followed by the kidneys (0.517 ± 0.125 mGy/MBq). The estimated overall effective dose for the administration of 111 MBq was 10.1 mSv (0.0913 ± 0.0118 mSv/MBq). In 6 patients, and in particular in 3 of 4 patients with negative [⁶⁸Ga]Ga-PSMA-11 PET/CT, at least one prostate cancer lesion was detected in [⁸⁹Zr]Zr-PSMA-617 PET/CT imaging at later time points. The majority of tumor lesions were first visible at 24 h p.i. with continuously increasing tumor-to-background ratio over time. All tumor lesions were detectable at 48 h and 72 h p.i.

Conclusion: [⁸⁹Zr]Zr-PSMA-617 PET/CT imaging is a promising new diagnostic tool with acceptable radiation exposure for patients with prostate cancer especially when [⁶⁸Ga]Ga-PSMA-11 PET/CT imaging fails detecting recurrent disease. The long half-life of ⁸⁹Zr enables late time point imaging (up to 72 h in our study) with increased tracer uptake in tumor lesions and higher tumor-to-background ratios allowing identification of lesions non-visible on [⁶⁸Ga]Ga-PSMA-11 PET/CT imaging.

Keywords: Biochemical recurrence; PET/CT; PSMA; Prostate cancer; Zirconium-89.

Fig. 1

Representative example (patient no. 2) A Maximum intensity projections at 4 time points post injection (p.i.) of [⁸⁹Zr]Zr-PSMA-617, B Respective SUV_max, SUV_peak and SUV_mean kinetics in normal organs (kidneys, liver, spleen, parotid gland, submandibular gland) and background (gluteal muscle)

Fig. 2

Biodistribution of [⁸⁹Zr]Zr-PSMA-617 with descriptive statistics (mean ± standard deviation) of A SUV_max, B SUV_peak, and C SUV_mean and D tissue-to-background ratio (TiBR) in normal organs at 1 h, 24 h, 48 h, and 72 h p.i.

Fig. 3

Maximum intensity projections (MIP) and transversal PET/CT slices of patient no. 6 (PSA 0.43 ng/ml) at 1 h (A), 24 h (B), 48 h (C), and 72 h (D) post injection (p.i.) of [⁸⁹Zr]Zr-PSMA-617. Red arrows point to a suspicious focal uptake in the left seminal vesicle bed showing increased tracer uptake at 24 h p.i., 48 h p.i., and 72 h p.i. compared to 1 h p.i., therefore considered as local recurrence. SUV_max at 1 h / 24 h / 48 h and 72 h p.i.: 7.04 / 21.27 / 21.09 / 19.19

Fig. 4

SUV_max (A) and tumor-to-background ratio (TBR) (B) of all tumor lesions at 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of [⁸⁹Zr]Zr-PSMA-617. LR, local recurrence; LNM, lymph node metastasis; PM, peritoneal metastasis

Fig. 5

Transversal slices of [⁸⁹Zr]Zr-PSMA-617 (right) and [⁶⁸Ga]Ga-PSMA-11 (left) PET/CT of 2 patients (patient no. 1 and 7) with PSMA-positive lesions detected by [⁸⁹Zr]Zr-PSMA-617 but unidentified by [⁶⁸Ga]Ga-PSMA-11. Red arrows point to suspected focal uptake. Patient no. 1 (PSA 1.92 ng/ml) with focal uptake (SUV_max 3.68) in the prostate bed considered as local recurrence. Patient no. 7 (PSA 0.68 ng/ml) with focal uptake (SUV_max 8.06) in a pelvic lymph node considered as lymph node metastasis

Fig. 6

Transversal slices of [⁸⁹Zr]Zr-PSMA-617 (right) and [⁶⁸Ga]Ga-PSMA-11 (left) PET/CT of 2 patients (patient no. 2 and 4) with undetermined PSMA-positive findings on [⁶⁸Ga]Ga-PSMA-11 PET/CT clarified by [⁸⁹Zr]Zr-PSMA-617 PET/CT. Green arrows point to pelvic tracer uptake (SUV_max 4.47) on [⁶⁸Ga]Ga-PSMA-11 PET/CT 1 h p.i. with no corresponding uptake on [⁸⁹Zr]Zr-PSMA-617 PET/CT, considered as unspecific uptake. Red arrows point to faint tracer uptake (SUV_max 2.06) in a peritoneal lesion on [⁶⁸Ga]Ga-PSMA-11 PET/CT 1 h p.i. with corresponding uptake (SUV_max 2.87) on [⁸⁹Zr]Zr-PSMA-617 PET/CT 48 h p.i. considered as peritoneal metastasis