Detection efficacy of [89Zr]Zr-PSMA-617 PET/CT in [68Ga]Ga-PSMA-11 PET/CT-negative biochemical recurrence of prostate cancer

Rationale In patients with biochemical recurrence of prostate cancer (BCR), preliminary data suggest that prostate-specifc membrane antigen (PSMA) ligand radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h), which allow imaging≥24 h post-injection, detect suspicious lesions that are missed when using tracers incorporating short-lived radionuclides. Materials and methods To confrm [ 89Zr]Zr-PSMA-617 positron emission tomography/computed tomography (PET/CT) detection efcacy regarding such lesions, and compare quality of 1-h, 24-h, and 48-h [ 89Zr]Zr-PSMA-617 scans, we retrospectively analyzed visual fndings and PET variables refecting lesional [ 89Zr]Zr-PSMA-617 uptake and lesion-to-background ratio. The cohort comprised 23 men with BCR post-prostatectomy, median (minimum–maximum) prostate-specifc antigen (PSA) 0.54 (0.11–2.50) ng/mL, and negative [ 68Ga]Ga-PSMA-11 scans 40±28 d earlier. Primary endpoints were percentages of patients with, and classifcations of, suspicious lesions. Results Altogether, 18/23 patients (78%) had 36 suspicious lesions (minimum–maximum per patient: 1–4) on both 24-h and 48-h scans (n=33 lesions) or only 48-h scans (n=3 lesions). Only one lesion appeared on a 1-h scan. Lesions putatively represented local recurrence in 11 cases, and nodal or bone metastasis in 21 or 4 cases, respectively; 1/1 lesion was histologically confrmed as a nodal metastasis. In all 15 patients given radiotherapy based on [ 89Zr]Zr-PSMA-617 PET/CT, PSA values decreased after this treatment. Comparison of PET variables in 24-h vs 48-h scans suggested no clear superiority of either regarding radiotracer uptake, but improved lesion-to-background ratio at 48 h. Conclusions In men with BCR and low PSA, [ 89Zr]Zr-PSMA-617 PET/CT seems efective in fnding prostate malignancy not seen on [ 68Ga]Ga-PSMA-11 PET/CT. The higher detection rates and lesion-to-background ratios of 48-h scans versus 24-h scans suggest that imaging at the later time may be preferable. Prospective study of [ 89Zr]Zr-PSMA-617 PET/CT is warranted

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

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 (T1/2=78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our frst 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 efective 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 frst 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 identifcation of lesions non-visible on [ 68Ga]Ga-PSMA-11 PET/CT imaging

Change in total lesion PSMA (TLP) during [177Lu]Lu-PSMA-617 radioligand therapy predicts overall survival in patients with mCRPC: monocentric evaluation of a prospective registry

Purpose This study investigates imaging response of [ 177Lu]Lu-PSMA-617 radioligand therapy (RLT) based on the wholebody parameter total lesion PSMA (TLP), derived by PSMA-PET/CT and refecting the total tumor burden, in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a prospective registry (NCT 04833517). Methods A total of n = 102 mCRPC patients received a [ 68Ga]Ga-PSMA-11 PET/CT at baseline and after two cycles of PSMA-RLT, in which TLP was measured by using a semi-automated tumor segmentation. TLP was defned as the summed products of volume and uptake (∑ Volume × SUVmean) of all tumor lesions. The Kaplan-Meier method was used to determine the most appropriate ∆TLP thresholds for classifcation into partial remission (PR), stable disease (SD), and progressive disease (PD) regarding overall survival (OS). Furthermore, we analyzed criteria that are also frequently used in established response frameworks, such as the occurrence of new metastases as independent criterion (I) or in combination with change in tumor burden (II), and the change in PSA serum value (III). Results For the ∆TLP thresholds −30%/+30% (and also for higher thresholds, −40%/+40% or −50%/+50%), signifcant diferences between all three response categories became apparent (PR/PD: p = 0.001; PR/SD: p = 0.001; SD/PD: p = 0.018). Including the development of new metastases as independent criterion of PD, there was no signifcant diference in OS between SD and PD (p = 0.455), neither when applied in combination with TLP (p = 0.191). Similarly, signifcant diferentiation between SD and PD was not achieved by PSA serum value (p = 0.973). Conclusion In the largest monocentric study to date, TLP is shown to be a qualifed prognostic biomarker, applying ∆TLP thresholds of −30%/+30%. It signifcantly diferentiated between PR, SD, and PD, whereas other response criteria did not diferentiate SD vs. PD. Using TLP, the development of new metastases is not a required information for predicting OS

[89Zr]Zr-PSMA-617 PET/CT characterization of indeterminate [68Ga]Ga-PSMA-11 PET/CT findings in patients with biochemical recurrence of prostate cancer: lesion-based analysis

Abstract Background The state-of-the-art method for imaging men with biochemical recurrence of prostate cancer (BCR) is prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) with tracers containing short-lived radionuclides, e.g., gallium-68 (68Ga; half-life: ∼67.7 min). However, such imaging not infrequently yields indeterminate findings, which remain challenging to characterize. PSMA-targeted tracers labeled with zirconium-89 (89Zr; half-life: ∼78.41 h) permit later scanning, which may help in classifying the level of suspiciousness for prostate cancer of lesions previously indeterminate on conventional PSMA-targeted PET/CT. Methods To assess the ability of [89Zr]Zr-PSMA-617 PET/CT to characterize such lesions, we retrospectively analyzed altogether 20 lesions that were indeterminate on prior [68Ga]Ga-PSMA-11 PET/CT, in 15 men with BCR (median prostate-specific antigen: 0.70 ng/mL). The primary endpoint was the lesions’ classifications, and secondary endpoints included [89Zr]Zr-PSMA-617 uptake (maximum standardized uptake value [SUVmax]), and lesion-to-background ratio (tumor-to-liver ratio of the SUVmax [TLR]). [89Zr]Zr-PSMA-617 scans were performed 1 h, 24 h, and 48 h post-injection of 123 ± 19 MBq of radiotracer, 35 ± 35 d post-[68Ga]Ga-PSMA-11 PET/CT. Results Altogether, 6/20 previously-indeterminate lesions (30%) were classified as suspicious (positive) for prostate cancer, 14/20 (70%), as non-suspicious (negative). In these two categories, [89Zr]Zr-PSMA-617 uptake and lesional contrast showed distinctly different patterns. In positive lesions, SUVmax and TLR markedly rose from 1 to 48 h, with SUVmax essentially plateauing at high levels, and TLR further steeply increasing, from 24 to 48 h. In negative lesions, uptake, when present, was very low, and decreasing, while contrast was minimal, from 1 to 48 h. No adverse events or clinically-relevant vital signs changes related to [89Zr]Zr-PSMA-617 PET/CT were noted during or ~ 4 weeks after the procedure. Conclusions In men with BCR, [89Zr]Zr-PSMA-617 PET/CT may help characterize as suspicious or non-suspicious for prostate cancer lesions that were previously indeterminate on [68Ga]Ga-PSMA-11 PET/CT. Trial registration Not applicable