<Superscript>68</Superscript>Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer

Objectives

We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand ⁶⁸Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and ⁶⁸Ga-PSMA-11 PET parameters is also investigated.

Methods

31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0 years) were enrolled in the analysis. The median PSA value was 2.0 ng/mL (range?=?0.1 – 130.0 ng/mL) and the median Gleason score was 7 (range?=?5 – 9). 8/31 (25.8 %) of the included patients had a PSA value?<?0.5 ng/ml. All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

22/31 patients (71.0 %) were ⁶⁸Ga-PSMA-11-positive, while 9/31 (29.0 %) patients were ⁶⁸Ga-PSMA-11-negative. The median PSA value in the ⁶⁸Ga-PSMA-11-positive group was significantly higher (median?=?2.35 ng/mL; range?=?0.19 – 130.0 ng/mL) than in the ⁶⁸Ga-PSMA-11-negative group (median value: 0.34 ng/mL; range?=?0.10 – 4.20 ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUV_average?=?12.4 (median?=?9.0; range?=?2.2 – 84.5) and mean SUV_max = 18.8 (median?=?14.1; range?=?3.1 – 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K₁?=?0.26, k₃?=?0.30, influx?=?0.14 and FD?=?1.24. Time–activity curves derived from PC-recurrence indicative lesions revealed an increasing ⁶⁸Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant, correlation between PSA levels and the number of lesions detected on ⁶⁸Ga-PSMA-11 PET/CT (r?=?0.54) and between PSA levels and SUV_average (r?=?0.48) or SUV_max (r?=?0.44).

Conclusions

Ga-PSMA-11 PET/CT demonstrated an overall detection rate of 71.0 % 60 min p.i. of the radiotracer in a mixed patient population with respect to PSA levels and including patients with very low PSA values. Higher PSA values were associated with a higher detection rate. The tracer uptake in PC-recurrence-indicative lesions is increasing during the 60 minutes of dynamic PET acquisition.

     

Local recurrence of prostate cancer after radical prostatectomy is at risk to be missed in <Superscript>68</Superscript>Ga-PSMA-11-PET of PET/CT and PET/MRI: comparison with mpMRI integrated in simultaneous PET/MRI

Purpose

The positron emission tomography (PET) tracer ⁶⁸Ga-PSMA-11, targeting the prostate-specific membrane antigen (PSMA), is rapidly excreted into the urinary tract. This leads to significant radioactivity in the bladder, which may limit the PET-detection of local recurrence (LR) of prostate cancer (PC) after radical prostatectomy (RP), developing in close proximity to the bladder. Here, we analyze if there is additional value of multi-parametric magnetic resonance imaging (mpMRI) compared to the ⁶⁸Ga-PSMA-11-PET-component of PET/CT or PET/MRI to detect LR.

Methods

One hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybrid ⁶⁸Ga-PSMA-11-PET/CT_low-dose (1 h p.i.) and -PET/MRI (2-3 h p.i.) including a mpMRI protocol of the prostatic bed. The comparison of both methods was restricted to the abdomen with focus on LR (McNemar). Bladder-LR distance and recurrence size were measured in axial T2w-TSE. A logistic regression was performed to determine the influence of these variables on detectability in ⁶⁸Ga-PSMA-11-PET. Standardized-uptake-value (SUV_mean) quantification of LR was performed.

Results

There were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p?=?0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p?=?0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p?=?0.84), mean size was 1.7?±?0.69 cm long axis, 1.2?±?0.46 cm short-axis. SUV_mean in nine men was 8.7?±?3.7 (PET/CT) and 7.0?±?4.2 (PET/MRI) but could not be quantified in the remaining nine cases (obliterated by bladder).

Conclusion

The present study demonstrates additional value of hybrid ⁶⁸Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to ^{the 68}Ga-PSMA-11-PET/CT_low-dose for patients with LR of PC.

     

Reproducibility of standardized uptake values of same-day randomized <Superscript>68</Superscript>Ga-PSMA-11 PET/CT and PET/MR scans in recurrent prostate cancer patients

Objective

Positron emission tomography in association with magnetic resonance imaging (PET/MR) and ⁶⁸Ga-PSMA-11 has shown superior detection in recurrent prostate cancer patients as compared to PET/computed tomography (PET/CT). There are, however, several technological differences between PET/CT and PET/MR systems which affect the PET image quality. The objective of this study was to assess the reproducibility of PET/CT and PET/MR SUV’s in recurrent prostate cancer patients. We randomized the patients regarding the order of the PET/CT and PET/MR scans to reduce the influence of tracer uptake as a function of time.

Methods

Thirty patients, all with biochemical recurrence after radical prostatectomy, underwent whole-body PET/CT and PET/MR scans after intravenous injection of a single dose of ⁶⁸Ga-PSMA-11. Fifteen patients underwent PET/CT first and 15 patients underwent PET/MR first. Volumes of interest on tumor lesions were outlined and maximum standardized uptake value (SUVmax) corrected for lean body mass was calculated. Correlation and agreement between scans were assessed by generalized linear mixed-effects models and Bland–Altman analysis. The association between SUV, patient characteristics and imaging parameters was assessed.

Results

Eighteen of the 30 evaluated patients had at least one positive lesion, giving an overall detection rate of 60%. In total, there were 34 visible lesions: 5 local recurrences, 22 lymph node metastases and 7 bone metastases. One group acquired PET/CT and PET/MR at median time points of 63.0 and 159.0 min, while the other group acquired PET/MR and PET/CT at median time points of 92.0 and 149.0 min. SUVmax between scans was linearly correlated, described by the equation Y(PET/CT SUVmax)?=?0.75?+?1.00?×?(PET/MR SUVmax), on average 20% higher on PET/CT than on PET/MR. SUV associated significantly only with type of lesion, scan time post-injection and acquisition time per bed position.

Conclusions

SUVmax from PET/CT and PET/MR are linearly correlated, on average 20% higher on PET/CT than on PET/MR and should, therefore, not be used interchangeably in patient follow-up.

     

<Superscript>68</Superscript>Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer

Purpose

We aimed at evaluating the role of ⁶⁸Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer.

Methods

A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [⁶⁸Ga]Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA-11). Quantitative assessment of all 641 ⁶⁸Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores.In 23 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels.

Results

PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P?<?0.0001) and TL-PSMA was significantly different for different Gleason scores. The agreement rate between TL-PSMA derived from PET and biochemical response was 87% (95% confidence interval, 0.66–0.97; Cohen’s κ?=?0.78; P?< 0.01) and, thus, higher than for SUVmax, which was 74% (95% CI, 0.52–0.90; κ?=?0.55; P?< 0.01). Furthermore, agreement with PSA was higher for TL-PSMA and SUVmax than for CT-based response evaluation. Discordant findings between PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT.

Conclusion

⁶⁸Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with ⁶⁸Ga-PSMA-11.

     

Comparison of <Superscript>68</Superscript>Ga-labelled PSMA-11 and <Superscript>11</Superscript>C-choline in the detection of prostate cancer metastases by PET/CT

Purpose

Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using ¹¹C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand ⁶⁸Ga-PSMA-11 with ¹¹C-choline in patients with primary and recurrent prostate cancer.

Methods

123 patients underwent a whole-body PET/CT examination using ⁶⁸Ga-PSMA-11 and ¹¹C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging.

Results

In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using ⁶⁸Ga-PSMA-11 showed a significantly higher uptake and detection rate than ¹¹C-choline PET. Also ⁶⁸Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients’ biochemical relapse. Significantly more bone lesions were detected by ⁶⁸Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per ¹¹C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by ⁶⁸Ga-PSMA-11 PET.

Conclusion

Thus, PET using ⁶⁸Ga-PSMA-11 showed a higher detection rate than ¹¹C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers.

     

Intra-individual comparison of <Superscript>68</Superscript>Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer

Purpose

Multi-parametric magnetic resonance imaging (MP-MRI) is currently the most comprehensive work up for non-invasive primary tumor staging of prostate cancer (PCa). Prostate-specific membrane antigen (PSMA)-Positron emission tomography–computed tomography (PET/CT) is presented to be a highly promising new technique for N- and M-staging in recurrent PCa-patients. The actual investigation analyses the potential of ⁶⁸Ga-PSMA11-PET/CT to assess the extent of primary prostate cancer by intra-individual comparison to MP-MRI.

Methods

In a retrospective study, ten patients with primary PCa underwent MP-MRI and PSMA-PET/CT for initial staging. All tumors were proven histopathological by biopsy. Image analysis was done in a quantitative (SUVmax) and qualitative (blinded read) fashion based on PI-RADS. The PI-RADS schema was then translated into a 3D-matrix and the euclidian distance of this coordinate system was used to quantify the extend of agreement.

Results

Both MP-MRI and PSMA-PET/CT presented a good allocation of the PCa, which was also in concordance to the tumor location validated in eight-segment resolution by biopsy. An Isocontour of 50 % SUVmax in PSMA-PET resulted in visually concordant tumor extension in comparison to MP-MRI (T2w and DWI). For 89.4 % of sections containing a tumor according to MP-MRI, the tumor was also identified in total or near-total agreement (euclidian distance ≤1) by PSMA-PET. Vice versa for 96.8 % of the sections identified as tumor bearing by PSMA-PET the tumor was also found in total or near-total agreement by MP-MRI.

Conclusions

PSMA-PET/CT and MP-MRI correlated well with regard to tumor allocation in patients with a high pre-test probability for large tumors. Further research will be needed to evaluate its value in challenging situation such as prostatitis or after repeated negative biopsies.

     

Effects of arm truncation on the appearance of the halo artifact in <Superscript>68</Superscript>Ga-PSMA-11 (HBED-CC) PET/MRI

Purpose

PSMA ligand imaging with hybrid PET/MRI scanners could be an integral part of the clinical routine in the future. However, the first study about this novel method revealed a severe photopenic artifact (“halo artifact”) around the urinary bladder causing significantly reduced tumor visibility. The aim of this evaluation was to analyze the role of arm truncation on the appearance of the halo artifact in ⁶⁸Ga-PSMA-11 PET/MRI hypothesizing that this influences the appearance.

Methods

Twenty-seven consecutive patients were subjected to ⁶⁸Ga-PSMA-11 PET/CT (1 h p.i.) followed by PET/MRI (3 h p.i.). PET/MRI was first started with scans of the abdomen to pelvis with arms positioned up above the head. Immediately thereafter, additional scans from the pelvis to abdomen were conducted with arms positioned down beside the trunk. All investigations were first analyzed separately and then compared with respect to tumor detection and tumor uptake (SUV) as well as the presence and intensity of the halo artifact. The Wilcoxon signed rank test was used to determine statistical differences including Bonferroni correction.

Results

The halo was significantly reduced if the arms were elevated. Lesions inside the halo artifact (n = 16) demonstrated significantly increased SUVmean (p = 0.0007) and SUVmax (p = 0.0024) with arms positioned up. The halo appearance and intensity was not dependent on the total activity and activity concentration of the urinary bladder.

Conclusion

Positioning the arms down was shown to be significantly associated with the appearance of the halo artifact in PET/MRI. Positioning the arms up above the head can significantly reduce the halo artifact, thereby detecting more tumor lesions.

     

[<Superscript>11</Superscript>C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy

Purpose The aim of this study was to assess the accuracy and clinical impact of [¹¹C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy. Methods Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse underwent [¹¹C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [¹¹C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity uptake value (SUV_max) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact of the PET/CT study was determined. Results [¹¹C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUV_max of local recurrence was 3.0 (median, range 0.6–7.4) and 1.1 (0.4–1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9–3.7). Area under the ROC curve for detecting relapse was 0.90 ± 0.05 and 0.83 ± 0.06 for visual evaluation and SUV_max, respectively. Sensitivity and specificity of [¹¹C]choline PET/CT were 0.73 and 0.88, respectively. [¹¹C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median, 0.8–3.2 range) follow-up. Conclusions Focally increased [¹¹C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy.     

<Superscript>68</Superscript>Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients

Purpose

We studied the usefulness of ⁶⁸Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment.

Methods

Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. ⁶⁸Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150?±?50 MBq of ⁶⁸Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, ⁶⁸Ga-PSMA PET/CT scans were compared with negative ¹⁸F-choline PET/CT scans routinely performed up to 1 month previously.

Results

From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44–92 years) and their median PSApet was 0.83 ng/ml (range 0.003–80.0 ng/ml). ⁶⁸Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P?<?0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on ⁶⁸Ga-PSMA PET/CT.

Conclusion

We confirmed the value of ⁶⁸Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

     

<Superscript>68</Superscript>Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary results on differences between black and white South-Africans

Purpose

The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in ⁶⁸Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients.

Methods

⁶⁸Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined.

Results

Ninety-three out of 95 PPC where readily identified on ⁶⁸Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005).

Conclusion

SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.

     

Comparison of [<Superscript>68</Superscript>Ga]Ga-PSMA-11 PET/CT with [<Superscript>18</Superscript>F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy

Aim

The purpose of this study was to investigate the diagnostic performance of ⁶⁸Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [¹⁸F]sodium fluoride (¹⁸F-NaF) PET/CT.

Methods

Sixteen metastatic PC patients with known skeletal metastases, who underwent both ⁶⁸Ga-PSMA-11 PET/CT and ¹⁸F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on ¹⁸F-NaF PET and ⁶⁸Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV_max) and compared to background activity of normal bone. In addition, SUV_max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan.

Results

In contrast to 468 PET-positive lesions suggestive of bone metastases on ¹⁸F-NaF PET, only 351 of the lesions were also judged positive on ⁶⁸Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on ¹⁸F-NaF PET compared to ⁶⁸Ga-PSMA-11 PET, showing a median SUV_max of 27.0 and 6.0, respectively (p?<?0.001). Background activity of normal bone was lower on ⁶⁸Ga-PSMA-11 PET, with a median SUV_max of 1.0 in comparison to 2.7 on ¹⁸F-NaF PET; however, tumour to background ratio was significantly higher on ¹⁸F-NaF PET (9.8 versus 5.9 on ⁶⁸Ga-PSMA-11 PET; p?=?0.042). Based on morphologic lesion characterisation on CT, ¹⁸F-NaF PET revealed median SUV_max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on ⁶⁸Ga-PSMA-11 PET median SUV_max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between¹⁸F-NaF PET and ⁶⁸Ga-PSMA-11 PET was significantly higher in osteosclerotic (p?<?0.001) and lesions not visible on CT (p?=?0.012).

Conclusion

In comparison to ⁶⁸Ga-PSMA-11 PET/CT, ¹⁸F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that ⁶⁸Ga-PSMA-11 PET should be combined with ¹⁸F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.

     

Prospective comparison of <Superscript>68</Superscript>Ga-PSMA PET/CT, <Superscript>18</Superscript>F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer

Purpose

To prospectively compare diagnostic accuracies for detection of bone metastases by ⁶⁸Ga-PSMA PET/CT, ¹⁸F-NaF PET/CT and diffusion-weighted MRI (DW₆₀₀-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR).

Methods

Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent ⁶⁸Ga-PSMA PET/CT, a ¹⁸F-NaF PET/CT and a DW₆₀₀-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm²). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic.

Results

Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for ⁶⁸Ga-PSMA PET/CT (n?=?68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for ¹⁸NaF PET/CT (n?=?67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW₆₀₀-MRI (n?=?60 patients). The diagnostic performance of DW₆₀₀-MRI was significantly lower than that of ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT for diagnosing bone metastases (p?<?0.01), and no significant difference in the AUC was seen between ⁶⁸Ga-PSMA PET/CT and ¹⁸NaF PET/CT (p?=?0.65).

Conclusion

⁶⁸Ga-PSMA PET/CT and ¹⁸F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW₆₀₀-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

     

Patterns of relapse as determined by <Superscript>68</Superscript>Ga-PSMA ligand PET/CT after radical prostatectomy

Purpose

To evaluate the patterns of relapse and impact on the intended treatment when using ⁶⁸Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT).

Methods

In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a ⁶⁸Ga-PSMA ligand PET/CT for planning of sRT.

Results

PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0?ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUV_peak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0?Gy.

Conclusion

Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a ⁶⁸Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0?ng/mL, a ⁶⁸Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.

     

Evaluation of <Superscript>68</Superscript>Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Objectives

To compare the diagnostic performance of ⁶⁸Ga-DOTATOC PET/MRI and ⁶⁸Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET).

Methods

Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar’s chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson’s correlation coefficient (r).

Results

According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p?=?0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p?=?0.031). SUVmax was strongly correlated (r?=?0.86; p?<?0.001) and did not differ significantly (p?=?0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p?<?0.01).

Conclusions

Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to ⁶⁸Ga-DOTATOC PET/CT in whole-body staging of NET patients.

Key Points

? ⁶⁸ Ga-DOTATOC PET/MRI correctly identified more NET lesions than ⁶⁸ Ga-DOTATOC PET/CT. ? ⁶⁸ Ga-DOTATOC PET/MRI provides better NET lesion conspicuity than ⁶⁸ Ga-DOTATOC PET/CT. ? SUVmax values from the two modalities are strongly correlated and do not differ significantly.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer

Purpose

The aims of this retrospective analysis were to compare ⁶⁸Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative ⁶⁸Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.

Methods

In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05.

Results

In total, 168 ⁶⁸Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both ⁶⁸Ga-PSMA PET-positive and CT-positive, 65 were only ⁶⁸Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more ⁶⁸Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several ⁶⁸Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV_average and SUV_max), its transport rate from plasma to the interstitial/intracellular compartment (K₁), its rate of binding to the PSMA receptor and its internalization (k₃), its influx rate (K_i), and its distribution heterogeneity.

Conclusion

⁶⁸Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. ⁶⁸Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several ⁶⁸Ga-PSMA PET parameters.

     

Diagnostic performance of <Superscript>18</Superscript>F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer

Purpose

The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially ⁶⁸Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). ¹⁸F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced ¹⁸F-PSMA-1007 in patients with recurrent PCa.

Methods

This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75?±?7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338?±?44.31 MBq ¹⁸F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a ¹⁸F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.

Results

Of the 100 patients, 95 (95%) showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04–41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and?>?2.0 ng/ml, respectively. The median GS was 7 (range 5–10). The majority of patients (70) with a GS available had a score in the range 7–9. The rate of pathological scans in these patients was 93% (65/70). The median SUV_max values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml, respectively. The median SUV_max in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.

Conclusion

¹⁸F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological ¹⁸F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.

     

MRI versus <Superscript>68</Superscript>Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer

Purpose

Multiparametric magnetic resonance imaging (mpMRI) is widely used in radiation treatment planning of primary prostate cancer (PCA). Focal dose escalation to the dominant intraprostatic lesions (DIPL) may lead to improved PCA control. Prostate-specific membrane antigen (PSMA) is overexpressed in most PCAs. ⁶⁸Ga-labelled PSMA inhibitors have demonstrated promising results in detection of PCA with PET/CT. The aim of this study was to compare ⁶⁸Ga-PSMA PET/CT with MRI for gross tumour volume (GTV) definition in primary PCA.

Methods

This retrospective study included 22 patients with primary PCA analysed after ⁶⁸Ga-PSMA PET/CT and mpMRI. GTVs were delineated on MR images by two radiologists (GTV-MRIrad) and two radiation oncologists separately. Both volumes were merged leading to GTV-MRIint. GTVs based on PET/CT were delineated by two nuclear medicine physicians in consensus (GTV-PET). Laterality (left, right, and left and right prostate lobes) on mpMRI, PET/CT and pathological analysis after biopsy were assessed.

Results

Mean GTV-MRIrad, GTV-MRIint and GTV-PET were 5.92, 3.83 and 11.41 cm³, respectively. GTV-PET was significant larger then GTV-MRIint (p?=?0.003). The MRI GTVs GTV-MRIrad and GTV-MRIint showed, respectively, 40 % and 57 % overlap with GTV-PET. GTV-MRIrad and GTV-MRIint included the SUVmax of GTV-PET in 12 and 11 patients (54.6 % and 50 %), respectively. In nine patients (47 %), laterality on mpMRI, PET/CT and histopathology after biopsy was similar.

Conclusion

Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % – 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. ⁶⁸Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.

     

Prospective head-to-head comparison of <Superscript>11</Superscript>C-choline-PET/MR and <Superscript>11</Superscript>C-choline-PET/CT for restaging of biochemical recurrent prostate cancer

Purpose

Whole-body integrated ¹¹C-choline PET/MR might provide advantages compared to ¹¹C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases.

Materials and methods

Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR).

Results

Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml.Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6–86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min).

Conclusions

¹¹C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and interpretations between different readers are consistent. It provides a higher diagnostic value for detecting local recurrence compared to PET/CT with the advantage of substantial dose reduction. Drawbacks of PET/MR are a substantially longer imaging time and a slight inferiority in detecting bone and lymph node metastases in patients with PSA values >2 ng/ml. Thus, we suggest the use of ¹¹C-choline PET/MR especially for patients with low (≤2 ng/ml) PSA values, whereas PET/CT is preferable in the subgroup with higher PSA values.

     

Value of <Superscript>11</Superscript>C-choline PET and PET/CT in patients with suspected prostate cancer

Purpose: The value and limitations of ¹¹C-choline PET and PET/CT for the detection of prostate cancer remain controversial. The aim of this study was to investigate the diagnostic efficacy of ¹¹C-choline PET and PET/CT in a large group of patients with suspected prostate cancer. Methods: Fifty-eight patients with clinical suspicion of prostate cancer underwent ¹¹C-choline PET (25/58, Siemens ECAT Exact HR+) or PET/CT (33/58, Philips Gemini) scanning. On average, 500 MBq of ¹¹C-choline was administered intravenously. Studies were interpreted by raters blinded to clinical information and other diagnostic procedures. Qualitative image analysis as well as semiquantitative SUV measurement was carried out. The reference standard was histopathological examination of resection specimens or biopsy. Results: Prevalence of prostate cancer in this selected patient population was 63.8% (37/58). ¹¹C-choline PET and PET/CT showed a sensitivity of 86.5% (32/37) and a specificity of 61.9% (13/21) in the detection of the primary malignancy. With regard to metastatic spread, PET showed a per-patient sensitivity of 81.8% (9/11) and produced no false positive findings. Conclusion: Based on our findings, differentiation between benign prostatic changes, such as benign prostatic hyperplasia or prostatitis, and prostate cancer is feasible in the majority of cases when image interpretation is primarily based on qualitative characteristics. SUV_max may serve as guidance. False positive findings may occur due to an overlap of ¹¹C-choline uptake between benign and malignant processes. By providing functional information regarding both the primary malignancy and its metastases, ¹¹C-choline PET may prove to be a useful method for staging prostate cancer.