Combined model-based and patient-specific dosimetry for <Superscript>18</Superscript>F-DCFPyL,a PSMA-targeted PET agent

Purpose

Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for ¹⁸F-DCFPyL in nine patients with metastatic prostate cancer.

Methods

Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321?±?8 MBq (8.7?±?0.2 mCi) of¹⁸F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes.

Results

The highest calculated mean AD per unit administered activity of ¹⁸F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of ¹⁸F-DCFPyL was 0.017?±?0.002 mSv/MBq.

Conclusions

¹⁸F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models.

     

<Superscript>68</Superscript>Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

Background

To report on imaging findings using ⁶⁸Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.

Methods

⁶⁸Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.

Results

Out of 81 tumor lesions identified, 84% were identified on ⁶⁸Ga-PSMA-HBED-CC PET. ⁶⁸Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p?=?0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p?=?0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and ⁶⁸Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r?=?0.407, p?=?0.015).

Conclusions

⁶⁸Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

     

Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted <Superscript>18</Superscript>F-DCFPyL in peripheral ganglia

Objective

Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent ¹⁸F-DCFPyL.

Methods

A total of 98 patients who underwent ¹⁸F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV_max), and maximum standardized uptake value corrected to lean body mass (SUL_max) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV_max and SUL_max values by the mean uptake in the ascending aorta (Aorta_mean) and the right gluteus muscle (Gluteus_mean).

Results

Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated ¹⁸F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts.

Conclusion

As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of ¹⁸F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.

     

The accuracy of <Superscript>68</Superscript>Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer

Purpose

To assess the diagnostic accuracy of ⁶⁸Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging.

Methods

This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology.

Results

Data on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging.

Conclusions

PSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging.

     

The impact of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT on radiotherapy planning in patients with prostate cancer

Purpose

To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([⁶⁸Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Methods

A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [⁶⁸Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [⁶⁸Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [⁶⁸Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone.

Results

[⁶⁸Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [⁶⁸Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD.

Conclusion

[⁶⁸Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

     

Diagnostic potential of PET/CT using a <Superscript>68</Superscript>Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience

Purpose

To evaluate the diagnostic potential of whole-body PET/CT using a ⁶⁸Ga-labelled PSMA ligand in renal cell carcinoma (RCC).

Methods

Six patients with histopathologically proven RCC underwent ⁶⁸Ga-PSMA PET/CT. Each PET/CT scan was evaluated in relation to lesion count, location and dignity. SUVmax was measured in primary tumours and PET-positive metastases. Tumour-to-background SUVmax ratios (TBR_SUVmax) were calculated for primary RCCs in relation to the surrounding normal renal parenchyma. Metastasis-to-background SUVmax ratios (MBR_SUVmax) were calculated for PET-positive metastases in relation to gluteal muscle.

Results

Five primary RCCs and 16 metastases were evaluated. The mean SUVmax of the primary RCCs was 9.9?±?9.2 (range 1.7?–?27.2). Due to high uptake in the surrounding renal parenchyma, the mean TBR_SUVmax of the primary RCCs was only 0.2?±?0.3 (range 0.02?–?0.7). Eight metastases showed focal ⁶⁸Ga-PSMA uptake (SUVmax 9.9?±?8.3, range 3.4?–?25.6). The mean MBR_SUVmax of these PET-positive metastases was 11.7?±?0.2 (range 4.4?–?28.1). All PET-negative metastases were subcentimetre lung metastases.

Conclusion

⁶⁸Ga-PSMA PET/CT appears to be a promising method for detecting RCC metastases. However, no additional diagnostic value in assessing the primary tumour was found.

     

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.

     

The <Superscript>68</Superscript>Ga/<Superscript>177</Superscript>Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUV<Subscript>max</Subscript> values and absorbed dose estimates

Introduction

A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods

Ten consecutive mCRPC patients were selected for ¹⁷⁷Lu-PSMA617 therapy on the basis of PSMA-targeted ⁶⁸Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (⁶⁸Ga-PSMA-HBED-CC and ¹⁸F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1?±?0.3 GBq, range 5.4–6.5 GBq) given intravenously over 30 minutes, 9?±?1 weeks apart. PET/CT scans were compared to ¹⁷⁷Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed.

Results

¹⁷⁷Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4?±?1.9 Gy/GBq; range 1.1–7.2 Gy/GBq), lymph node (2.6?±?0.4 Gy/GBq; range 2.3–2.9 Gy/GBq) as well as liver (2.4?±?0.8 Gy/GBq; range 1.7–3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18?±?0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased ¹⁷⁷Lu-PSMA617 and ⁶⁸Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p?<?0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions.

Conclusion

Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following ¹⁷⁷Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

     

Comparison of bone scintigraphy and <Superscript>68</Superscript>Ga-PSMA PET for skeletal staging in prostate cancer

Purpose

The aim of our study was to compare the diagnostic performance of ⁶⁸Ga-PSMA PET and ^99mTc bone scintigraphy (BS) for the detection of bone metastases in prostate cancer (PC) patients.

Methods

One hundred twenty-six patients who received planar BS and PSMA PET within three months and without change of therapy were extracted from our database. Bone lesions were categorized into benign, metastatic, or equivocal by two experienced observers. A best valuable comparator (BVC) was defined based on BS, PET, additional imaging, and follow-up data. The cohort was further divided into clinical subgroups (primary staging, biochemical recurrence, and metastatic castration-resistant prostate cancer [mCRPC]). Additionally, subgroups of patients with less than 30 days delay between the two imaging procedures and with additional single-photon emission computed tomography (SPECT) were analyzed.

Results

A total of 75 of 126 patients were diagnosed with bone metastases. Sensitivities and specificities regarding overall bone involvement were 98.7–100 % and 88.2–100 % for PET, and 86.7–89.3 % and 60.8–96.1 % (p?<?0.001) for BS, with ranges representing results for ‘optimistic’ or ‘pessimistic’ classification of equivocal lesions. Out of 1115 examined bone regions, 410 showed metastases. Region-based analysis revealed a sensitivity and specificity of 98.8–99.0 % and 98.9–100 % for PET, and 82.4–86.6 % and 91.6–97.9 % (p?<?0.001) for BS, respectively. PSMA PET also performed better in all subgroups, except patient-based analysis in mCRPC.

Conclusion

Ga-PSMA PET outperforms planar BS for the detection of affected bone regions as well as determination of overall bone involvement in PC patients. Our results indicate that BS in patients who have received PSMA PET for staging only rarely offers additional information; however, prospective studies, including a standardized integrated x-ray computed tomography (SPECT/CT) protocol, should be performed in order to confirm the presented results.

     

<Superscript>18</Superscript>F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes

Purpose

PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low ¹⁸F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.

Methods

Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.

Results

Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.

Conclusions

Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.

     

<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.

     

Assessing the role of <Superscript>18</Superscript>F-FDG PET and <Superscript>18</Superscript>F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis

Purpose

Twelve years ago a meta-analysis evaluated the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of ¹⁸F-FDG PET/CT and determine if there is added value when compared to PET.

Methods

A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of ¹⁸F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included.

Results

Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The ¹⁸F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively).

Conclusion

¹⁸F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

     

Comparison of standard and delayed imaging to improve the detection rate of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer

Purpose

The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [⁶⁸Ga]PSMA I&T.

Methods

240 patients who underwent a [⁶⁸Ga]PSMA I&T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging.

Results

The overall detection rates of [⁶⁸Ga]PSMA I&T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P?<?0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [⁶⁸Ga]PSMA I&T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease.

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study.

     

<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.

     

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [<Superscript>68</Superscript>Ga]PSMA I&amp;T and comparison with published data of [<Superscript>68</Superscript>Ga]PSMA HBED-CC

Purpose

To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [⁶⁸Ga]PSMA I&T and to compare it with published detection rates of [⁶⁸Ga]PSMA HBED-CC.

Methods

We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [⁶⁸Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [⁶⁸Ga]PSMA I&T were statistically compared with published detection rates of [⁶⁸Ga]PSMA HBED-CC using exact Fisher’s test.

Results

Median PSA was 0.81 (range: 0.01 – 128) ng/mL. In 58/83 patients (70 %) at least one [⁶⁸Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [⁶⁸Ga]PSMA I&T and published detection rates of [⁶⁸Ga]PSMA HBED-CC (all

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [⁶⁸Ga]PSMA HBED-CC.

     

<Superscript>68</Superscript>Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with <Superscript>111</Superscript>In-octreotide SPECT/CT and conventional imaging

Purpose

The aim of this study was to prospectively compare the detection rate of ⁶⁸Ga-DOTATATE PET-CT with ¹¹¹In-octreotide SPECT-CT and conventional imaging (CI) in medullary thyroid carcinoma (MTC) patients with increased calcitonin (Ctn) levels but negative CI after thyroidectomy.

Methods

Fifteen patients with raised Ctn levels and/or CI evidence of recurrence underwent ⁶⁸Ga-DOTATATE PET-CT, ¹¹¹In-octreotide SPECT-CT and CI. Histopathology, CI and biochemical/clinical/imaging follow-up were used as the reference standard. PET/CT, SPECT/CT and CI were compared in a lesion-based and organ-based analysis.

Results

PET/CT evidenced recurrence in 14 of 15 patients. There were 13 true positive (TP), 1 true negative (TN), 1 false positive (FP) and no false negative (FN) cases, resulting in a sensitivity and accuracy of 100% and 93%. SPECT/CT was positive in 6 of 15 cases. There were 6 TP, 2 TN, 7 FN and no FP cases, resulting in a sensitivity of 46% and accuracy of 53%. CI procedures detected tumor lesions in 14 of 15 patients. There were 13 TP, 1TN, 1 FP and no FN cases with a sensitivity of 100% and accuracy of 93%.A significantly higher number of lesions was detected by PET/CT (112 lesions, p = 0.005) and CI (109 lesions, p = 0.005) in comparison to SPECT/CT (16 lesions). There was no significant difference between PET/CT and CI for the total number of detected lesions (p = 0.734). PET/CT detected more lesions than SPECT/CT regardless of the organ. PET/CT detected more bone lesions but missed some neck nodal metastases evidenced by CI. The number of lesions per region demonstrated by PET/CT and CI were similar in the other sites.

Conclusion

⁶⁸Ga-DOTATATE PET/CT is superior to ¹¹¹In-octreotide SPECT/CT for the detection of recurrent MTC demonstrating a significantly higher number of lesions. ⁶⁸Ga-DOTATATE PET/CT showed a superior detection rate compared to CI in demonstrating bone metastases.

     

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.

     

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.

     

Radiation dosimetry of <Superscript>68</Superscript>Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing

Purpose

The clinical introduction of ⁶⁸Ga-PSMA-11 (“HBED-CC”) ligand targeting the prostate-specific membrane antigen (PSMA) has been regarded as a significant step forward in the diagnosis of prostate cancer (PCa). In this study, we provide human dosimetry and data on optimal timing of PET imaging after injection.

Methods

Four patients with recurrent PCa were referred for ⁶⁸Ga-PSMA-11 PET/CT. Whole-body PET/CT_low-dose scans were conducted at 5 min, and 1, 2, 3, 4 and 5 h after injection of 152–198 MBq ⁶⁸Ga-PSMA-11. Organs of moderate to high uptake were used as source organs; their total activity was determined at all measured time points. Time–activity curves were created for each source organ as well as for the remainder. The radiation exposure of a ⁶⁸Ga-PSMA-11 PET was identified using the OLINDA-EXM software. In addition, tracer uptake was measured in 16 sites of metastases.

Results

The highest tracer uptake was observed in the kidneys, liver, upper large intestine, and the urinary bladder. Mean organ doses were: kidneys 0.262?±?0.098 mGy/MBq, liver 0.031?±?0.004 mGy/MBq, upper large intestine 0.054?±?0.041 mGy/MBq, urinary bladder 0.13?±?0.059 mGy/MBq. The calculated mean effective dose was 0.023?±?0.004 mSv/MBq (=0.085?±?0.015 rem/mCi). Most tumor lesions (n?=?16) were visible at 3 h p.i., while at all other time points many were not qualitatively present (10/16 visible at 1 h p.i.).

Conclusions

The mean effective dose of a ⁶⁸Ga-PSMA-11 PET is 0.023 mSv/MBq. A 3-h delay after injection was optimal timing for ⁶⁸Ga-PSMA-11 PET/CT in this patient cohort.

     

Prognostic implications of <Superscript>62</Superscript>Cu-diacetyl-bis (<Emphasis Type="Italic">N</Emphasis><Superscript>4</Superscript>-methylthiosemicarbazone) PET/CT in patients with glioma

Objective

The potential of positron emission tomography/computed tomography using ⁶²Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of ⁶²Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG).

Method

56 patients with glioma of World Health Organization grade 2–4 were enrolled. All participants had undergone both ⁶²Cu-ATSM PET/CT and ¹⁸F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox’s proportional hazards model.

Results

Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using ⁶²Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using ⁶²Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p?<?0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using ⁶²Cu-ATSM PET/CT showed significant difference of progression-free survival (p?<?0.05).

Conclusions

⁶²Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to ¹⁸F-FDG PET/CT.