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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: Clin Nucl Med. 2019 Jun;44(6):431–438. doi: 10.1097/RLU.0000000000002575

Pretherapeutic 68Ga-PSMA-617 PET may indicate the dosimetry of 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 in main organs and tumor lesions

Jingnan Wang *,†, Jie Zang *,†, Hao Wang *,†, Qingxing Liu *,†, Fang Li *,†, Yansong Lin *,†, Li Huo *,†, Orit Jacobson ‡, Gang Niu ‡, Xinrong Fan , Zhaohui Zhu *,†, Xiaoyuan Chen ‡
PMCID: PMC6502681  NIHMSID: NIHMS1522169  PMID: 30985422

Abstract

Aim:

Combined 68Ga-PSMA-617 positron emission tomography (PET) imaging and 177Lu-PSMA-617 therapy is a precise targeted theranostic approach for patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of this study was to determine whether pretherapeutic standard uptake value (SUV) in 68Ga-PSMA-617 PET could indicate the effective dose in the main organs and absorbed dose in tumor lesions.

Methods:

Following institutional review board approval and informed consent, 9 patients with mCRPC were recruited and underwent 68Ga-PSMA-617 PET/computed tomography (CT) scans. Five patients received 177Lu-PSMA-617 (1.30–1.42 GBq, 35–38.4 mCi) and then underwent serial whole-body planar imaging and single-photon emission computed tomography/CT (SPECT/CT) imaging of both thoracic and abdominal regions at 0.5, 2, 24, 48, and 72 h time points. The other 4 patients received 177Lu-EB-PSMA-617 (0.80–1.1 GBq, 21.5–30 mCi) and then underwent the same imaging procedures at 2, 24, 72, 120, and 168 h time points. The effective dose in the main organs and the absorbed dose in tumor lesions were calculated. Detailed correlations between the pretherapeutic SUV in 68Ga-PSMA-617 PET and effective dose in the main organs, as well as absorbed dose in the tumor lesions were analyzed.

Results:

SUV of 68Ga-PSMA-617 PET was moderately correlated with effective dose in main organs (r = 0.610 for 177Lu-PSMA-617, r = 0.743 for 177Lu-EB-PSMA-617, both P < 0.001). SUV of tumor lesions in 68Ga-PSMA-617 PET had high correlation with those in 177Lu-PSMA-617 (r = 0.915, P < 0.001) and moderate correlation with those in 177Lu-EB-PSMA-617 (r = 0.611, P = 0.002).

Conclusions:

Pretherapeutic 68Ga-PSMA-617 PET may indicate the dosimetry of 177Lu-PSMA-617 and 177Lu-EB-PSMA-617. Both the effective dose in main organs and absorbed dose in tumor lesions correlate with SUV of 68Ga-PSMA-617 PET. This relationship may help select appropriate candidates for peptide receptor radionuclide therapy (PRRT). Further investigations of larger cohorts are needed to confirm these initial findings.

Keywords: 68Ga, 177Lu, prostate-specific membrane antigen (PSMA), metastatic castration-resistant prostate cancer (mCRPC), dosimetry

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death in the United States 1. Traditional diagnosis and treatment methods can no longer meet the clinical needs, especially in the management of patients with metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA) has attracted wide attention recently. PSMA expression on PC cells is directly correlated with androgen independence, metastasis formation and PC progression 2, 3. Radionuclide labeled molecules with high affinity for PSMA has become a new theranostic concept in PC management 4.

68Ga-PSMA-617 PET/CT or PET/MRI in detecting lymph node or bone metastases in PC has shown significantly higher sensitivity, specificity, and accuracy than traditional radiological means 5–9. These PSMA-expressing tumor lesions detected by 68Ga-PSMA-617 PET could be subsequently treated by 177Lu-PSMA-617. Several research groups have published favorable results of 177Lu-PSMA-617 dosimetry and treatment 10–13. According to these studies, the parotid glands, kidneys, and bone marrow were the critical organs with high radiation absorbed doses. More importantly, patients with mCRPC responded well to 177Lu-PSMA-617 treatment, with relieved clinical symptoms, prolonged survival time, and decreased serum PSA levels (>50%) in nearly half of the patients. Targeting PSMA provides a new “image and treat” strategy for precision management of PC patients 14.

Aiming to improve the pharmacokinetics and increase therapeutic efficacy, we previously developed EB-PSMA-617, which was synthesized by conjugating a truncated albumin-binding Evans blue (EB) molecule and 1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) chelator onto PSMA-617. Due to reversible albumin binding, the addition of EB moiety to 177Lu-PSMA-617 improved the pharmacokinetics of the radionuclide therapeutic agent, extended its blood half-life and tumor residence time and exhibited significantly higher uptake in xenograft tumors than PSMA-617 15.These resulted in relatively higher effective dose in main organs and absorbed dose in tumor lesions16. However, high inter- and intrapatient variability was observed. In PRRT for neuroendocrine tumors, a study reported that SUV of tumor lesions in pretherapeutic 68Ga-DOTA-TOC PET correlated with 177Lu absorbed doses 17. SUV may serve as an indicator for later-achieved absorbed dose and a predictor for the therapeutic outcome of PRRT 18. Similarly, the decisions for or against PRRT for mCRPC are presumably influenced and eventually based on pretherapeutic SUV of PET.

In this study, we retrospectively analyzed the patients who underwent pretherapeutic 68Ga-PSMA-617 PET and received low dose of 177Lu-EB-PSMA-617 or 177Lu-PSMA-617 in our institution with the same standardized protocol. We investigated the relationship between pretherapeutic SUV of PET and subsequently effective dose in main organs and absorbed dose in tumor lesions in both 177Lu-EB-PSMA-617 and 177Lu-PSMA-617.

PATIENTS AND METHODS

Patients and radiopharmaceuticals

The patient cohort was from our previous study16. This study was registered at clinicaltrials.gov (NCT03403595) and was approved by the Institute Review Board of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. During November 2017 and February 2018, we recruited 9 patients (mean age, 71 years; range, 60–81 years) with mCRPC. Among these patients, 4 were injected with 177Lu-EB-PSMA-617 and the other 5 with 177Lu-PSMA-617. For other details of these patients, inclusion and exclusion criteria, please refer to our previous study 16.

68Ga-PSMA-617, 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 were labeled according to the procedures reported previously 16. The radiolabeling yield of 177Lu-EB-PSMA-617 and 177Lu-PSMA-617 was more than 90% and their radiochemical purity was more than 95%.

PET acquisition and quantitative assessment

Intravenous injection of the tracer was performed with an injection activity of 111.1– 148.0 MBq. After 45–60 minutes, 68Ga-PSMA-617 PET/CT imaging (Siemens Medical Solutions, Erlangen, Germany) was performed. All PET acquisition was carried out in three-dimensional mode, 2 min per bed, 5–6 bed positions per patient. PET reconstruction used low-dose CT (120 kV, 35 mA, 512 × 512 matrix, 3-mm layer, 70 cm field of view) for attenuation correction and an ordered-subset expectation maximization iterative algorithm with 2 iterations and 8 subsets, with a 5-mm full width at half maximum postreconstruction Gaussian filter. A Siemens MMWP workstation was used for post-processing. Regions of interests (ROIs) were manually drawn including the main organs (heart, lung, pancreas, liver, spleen, stomach, muscle and salivary glands) and around the target tumor lesions (up to six lesions per patient) on PET slices by referring CT images. The post-processing workstation automatically calculated the volume of interest and SUVs.

SPECT/CT acquisition and quantitative assessment

After 68Ga-PSMA-617 PET acquisition, a single dose of 177Lu-PSMA-617 or 177Lu-EB-PSMA-617 was injected according to our standardized protocol. The time interval between 68Ga-PSMA-617 PET and 177Lu-EB-PSMA-617 (or 177Lu-PSMA-617) therapy was from 1 day to 7 days (2.3±2.2 days). No patients received other treatment during interval time and 177Lu therapy period. Five patients received intravenous administration of 177Lu-PSMA-617 1.30–1.42 GBq (35–38.4 mCi), followed by serial whole-body planar imaging and SPECT/CT of both thoracic and abdominal regions at 0.5, 2, 24, 48, and 72 h postinjection (p.i.). Another 4 patients received intravenous administration of 177Lu-EB-PSMA-617 0.80–1.1 GBq (21.5–30 mCi) with the same imaging acquisition procedures at 2, 24, 72, 120, and 168 h p.i. Images were obtained by the Philips Precedence scanner (Philips Healthcare, Andover, Massachusetts, USA) configured for 2-headed gamma camera, using a medium-energy general-purpose collimator with the energy window centered at 208 keV and a window width of 20%. For whole-body planar imaging, the acquisition matrix was 256 × 1024 and the scan speed was 15 cm per minute. For SPECT/CT, a procedure of 32 frames was performed, whose exposure time is 40 seconds per frame for each tomographic scan. SPECT reconstruction was performed using an iterative ordered-subset maximum-likelihood expectation maximization algorithm with 3 iterations and 8 subsets in the system’s software at the clinical workstation.

Data analysis and statistics

Dosimetry calculation was performed according to the European Association of Nuclear Medicine Dosimetry Guidance 19 and procedure reported previously. In order to calculate the dose concentration factor and voxel-based activity concentration, we utilized two radioactive sources with well-determined 177Lu activity and converted the factors in the volumes of interest to standardized uptake value (SUV). One of them was a cylindrical phantom, homogeneously filled with a solution containing a total of 370 MBq 177Lu activity, with a volume of 6.7 L and an internal diameter of 22 cm, which was used to calculate the SUV of major organs. The other was a cube phantom, homogeneously filled with a solution containing a total of 18.5 MBq 177Lu activity, with a volume of 20 mL, which was used to calculate the SUV of tumor lesions. For each main organ, the corresponding SUVs were used to generate the decay uncorrected time-activity curve. The volumes of individual organ were delineated on the serial CT images of the SPECT/CT slice by slice. SUVs were converted by referring the phantom. The effective doses were derived based on organ weight from the adult male phantom provided by the OLINDA/EXM v1.1 software (Vanderbilt University, Nashville, Tennessee, USA) 20, 21. The number of disintegrations for the main organs was obtained by fitting the data using a mono-exponential or a bi-exponential model provided by the software. Since tumor lesions were not included in the software, we assumed them to have a sphere morphology. Per patient, up to 6 lesions in relatively high uptake, large size and spherical shape were measured. The volumes of interests of tumor lesions were manually drawn slice by slice by referring the CT images. The areas under residence times-activity curve (AUC) (MBq-h/MBq/g) of tumor lesions were converted from SUVs and were calculated by the trapezoidal method in the Graphpad Prism software (Version 4.0, GraphPad Software, Inc.). The absorbed dose of tumor lesions was presented as areas under residence times-activity curve. We analyzed a total of 49 representative lesions (25 for 177Lu-PSMA-617 and 24 for 177Lu-EB-PSMA-617). In addition, the main organs (liver, spleen, lung, kidney and salivary glands) and corresponding tumor lesions were manually drawn on the 177Lu whole-body planar imaging. The activities were extracted from the ROIs using the geometric mean of both the anterior and posterior projections of the planar images. The effective doses of main organs were calculated from the residence time and activity values based on the adult male phantom by OLINDA/EXM v1.1 software. The effective dose of salivary glands and tumor lesions was calculated using the sphere model of the software. Detailed correlations between the pretherapeutic SUV in 68Ga-PSMA-617 PET with effective dose in main organs and with absorbed dose in tumor lesions were assessed using the Spearman rank correlation coefficient. Linear regression analysis was performed using SPSS software (IBM SPSS Statistics for Windows, version 21.0; Armonk, NY). All tests were two sided, and a P-value<0.05 was considered statistically significant. All quantitative data were expressed as mean ± standard deviation.

RESULTS

The representative images of patients are shown in Figure 1 and 2. In this study, the SUVmean in 68Ga-PSMA-617 PET, 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 SPECT of the main organs including the heart, lung, pancreas, liver, spleen, stomach, and muscle were measured in each patient. Linear regression analysis (Fig. 3) showed that the SUVmean of main organs in 68Ga-PSMA-617 PET and SUVmean in 177Lu-PSMA-617 SPECT/CT exhibited linear correlation at early time points p.i. (R2 = 0.827 at 0.5 h). However, for 177Lu-EB-PSMA-617, the linear relationship was not seen until late time points (R2 = 0.868 at 24 h).

FIGURE 1.

FIGURE 1.

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Representative 68Ga-PSMA PET/CT maximum intensity projection image and SPECT whole-body posterior planar images of an 81-year-old patient in 177Lu-PSMA group. (A) 68Ga-PSMA PET/CT maximum intensity projection image and (B) subsequent SPECT whole-body posterior projection images at different acquisition time points postinjection of 177Lu-PSMA.

FIGURE 2.

FIGURE 2.

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Representative 68Ga-PSMA PET/CT maximum intensity projection image and SPECT whole-body posterior planar images of a 73-year-old patient in 177Lu-EB-PSMA group. (A) 68Ga-PSMA PET/CT maximum intensity projection image and (B) subsequent SPECT whole-body anterior projection images at different acquisition time points postinjection of 177Lu-EB-PSMA.

FIGURE 3.

FIGURE 3.

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Linear regression analysis of main organs PET SUVmean and SPECT SUVmean. (A) 177Lu-PSMA group, R2 = 0.827 at 0.5 h postinjection. (B) 177Lu-EB-PSMA group, R2 = 0.868 at 24 h postinjection.

Effective dose of 177Lu in each main organ per patient was calculated and reported in our previous study16. SUVmean in 68Ga-PSMA-617 PET and effective dose in the main organs derived from SPECT/CT had a moderately but highly statistically significant correlation with 177Lu-PSMA-617 (r = 0.610), and 177Lu-EB-PSMA-617 (r = 0.743), both P < 0.001 (Fig. 4). SUVmean in 68Ga-PSMA-617 PET showed moderate correlation (r = 0.694, P < 0.001) with the effective dose derived from the whole-body planar imaging in the 177Lu-PSMA-617 group and no correlation with that in the 177Lu-EB-PSMA-617 group.

FIGURE 4.

FIGURE 4.

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Relationship between main organs PET SUVmean and effective dose (mSv/MBq). (A) 177Lu-PSMA group, r = 0.610. (B) 177Lu-EB-PSMA group, r = 0.743. P<0.001 (Spearman rank correlation analysis) for each group.

For tumor lesions, a total of 49 lesions from 9 patients were included in the analysis (25 lesions for 177Lu-PSMA-617 and 24 lesions for 177Lu-EB-PSMA-617). For the 177Lu-PSMA-617 group, the average SUVmean and SUVmax values of tumor lesions in 68Ga-PSMA-617 PET were 9.45 ± 8.33 and 15.75 ± 14.17, respectively. For the 177Lu-EB-PSMA-617 group, the average SUVmean and SUVmax values were 11.21 ± 8.54 and 19.24 ± 14.45. No significant difference was found in these two groups (P = 0.36). The absorbed dose in tumor lesions derived from SPECT/CT was presented by the area under residence time-activity curve (AUCs), which was 0.0356 ± 0.0361 MBq-h/MBq/g for the 177Lu-PSMA-617 group and 0.0766 ± 0.0385 MBq-h/MBq/g for the 177Lu-EB-PSMA-617 group. There were also linear relationships (Fig. 5) between the SUVmean of tumor lesions in 68Ga-PSMA-617 PET and 177Lu-PSMA-617 SPECT at early time points postinjection (R2 = 837 at 2 h), and 177Lu-EB-PSMA-617 SPECT at late time points (R2 = 0.683 at 72 h).

FIGURE 5.

FIGURE 5.

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Linear regression analysis of tumor lesions PET SUVmean and SPECT SUVmean. (A) 177Lu-PSMA group, R2 = 0.837 at 2 h postinjection. (B) 177Lu-EB-PSMA group, R2 = 0.683 at 72 h postinjection.

SUV of tumor lesions in 68Ga-PSMA-617 PET highly correlated with the corresponding AUC derived from SPECT/CT in the 177Lu-PSMA-617 group (r = 0.915 for SUVmax and r = 0.907 for SUVmean, both P < 0.001) (Fig. 6), but moderately correlated with the absorbed dose derived from the planar imaging (r = 0.592 for SUVmax and r = 0.585 for SUVmean, both P = 0.002). In the 177Lu-EB-PSMA-617 group, the SUV moderately correlated with AUC of tumor lesions (r = 0.611 for SUVmax and r = 0.594 for SUVmean, both P = 0.002), but had no correlation with the absorbed dose derived from the whole-body planar imaging (r = 0.449 for SUVmax, P = 0.062 and r = 0.431 for SUVmean, P = 0.074).

FIGURE 6.

FIGURE 6.

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Relationship between tumor lesions PET SUV and absorbed dose. The absorbed dose was presented by the areas under residence time-activity curve (AUC) (MBq-h/MBq/g). (A) 177Lu-PSMA group, P<0.001 (Spearman rank correlation analysis). (B) 177Lu-EB-PSMA group, P = 0.002 (Spearman rank correlation analysis).

Examples of corresponding 68Ga-PSMA-617 PET, 177Lu-PSMA-617 and177Lu-EB-PSMA-617 SPECT and resulting AUCs of the target tumor lesions are presented in Figure 7 and 8.

FIGURE 7.

FIGURE 7.

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A representative 81-year-old patient in the 177Lu-PSMA group. (A) 68Ga-PSMA PET maximum intensity projection image shows multiple bone metastasis marked with arrows. (B) 177Lu-PSMA SPECT whole-body posterior projection image at 2 h postinjection shows the corresponding tumor lesions. (C) Transverse fused SPECT/CT slices show T11 (red arrow) and L1 (blue arrow) metastasis. (D) The respective time-activity curves are presented.

FIGURE 8.

FIGURE 8.

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A representative 73-year-old patient in the 177Lu-EB-PSMA group. (A) 68Ga-PSMA PET maximum intensity projection image shows multiple bone metastasis marked with arrows. (B) 177Lu-EB-PSMA SPECT whole-body posterior projection image at 72 h postinjection shows the corresponding tumor lesions. (C) Transverse fused SPECT/CT slices show T7 (red arrow) and left sacroiliac joint (blue arrow) metastasis. (D) The respective time-activity curves are presented.

DISCUSSION

This retrospective study on 9 patients (5 in the 177Lu-PSMA group, and 4 in the 177Lu-EB-PSMA-617 group) with mCRPC shows that pretherapeutic SUVs of main organs or tumor lesions in 68Ga-PSMA-617 PET may indicate the corresponding effective dose or absorbed dose of 177Lu treatment. Our correlation data confirm the relationship between diagnostic uptake and therapeutic dose within certain range, which may provide a preliminary basis for estimating maximal tolerable dose for radionuclide treatment and therapeutic efficacy.

There are individual variations in the radiation tolerance limits in normal organs. Dosimetry of the radiopharmaceuticals for radionuclide therapy is essential to assess possible toxicity and side effects 22. In this study, we found that SUVmean of main organs in pretherapeutic 68Ga-PSMA-617 PET may indicate the dosimetry of 177Lu therapy both in the 177Lu-PSMA and 177Lu-EB-PSMA-617 groups. SUV had a moderate but highly statistically significant correlation with effective dose in main organs. Moreover, SUVmean in 68Ga-PSMA-617 PET and SUVmean in 177Lu-PSMA-617 SPECT were linearly correlated at early time points, while for 177Lu-EB-PSMA-617, at late time points. This was consistent with our previous finding that 177Lu-EB-PSMA-617 (t1/2 = 143.9 h) has relatively longer circulation time than 177Lu-PSMA-617 (t1/2 = 5.6 h) due to the albumin binding feature of Evans blue.

The main excretion pathway of radiopharmaceuticals is the kidneys. In several recent studies, the kidneys were regarded as the dose-limiting organs 23–25, with the mean limiting administrable activity lying between 30 to 60 GBq, with large inter-individual variation 10. Our previous dosimetry results showed that the highest estimated radiation dose was also in the kidneys, 2.39 ± 0.69 mSv/MBq for 177Lu-EB-PSMA-617, about 6 times higher than that for 177Lu-PSMA (0.39 ± 0.06 mSv/MBq)16. As the kidneys are the elimination organs of radiopharmaceuticals, PET SUVs of the kidneys are affected by radioactive urine, which could bring measurement error. Thus, it is reasonable that kidneys should be excluded from the correlation study in Figure 4. However, if the kidneys were included in this correlation study, we found the degree of the correlation between SUVmean in 68Ga-PSMA-617 PET and effective dose of main organs seemed slightly higher, with r = 0.737 for 177Lu-PSMA-617 and r = 0.828 for 177Lu-EB-PSMA-617, both P<0.001 (Fig. 9). For the intestine, from our observation, there are high variations in the tracer uptake of intestine in the same patient, even if this patient underwent 68Ga-PSMA-617 PET/CT examination twice within two days followed by the same procedure. The SUV could not be measured accurately. Because the salivary glands were out of the SPECT/CT field, their effective doses were derived from 177Lu whole-body planar imaging by sphere model of the OLINDA/EXM v1.1 software (1.2500 ± 0.5100 mGy/MBq in 177Lu-PSMA-617 group and 6.4100 ± 1.4000 mGy/MBq in 177Lu-EB-PSMA-617 group).

FIGURE 9.

FIGURE 9.

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Relationship between main organs (including the kidneys) PET SUVmean and effective dose (mSv/MBq). (A) 177Lu-PSMA group, r=0.737. (B) 177Lu-EB-PSMA group, r = 0.828. P<0.001 (Spearman rank correlation analysis) for each group.

As a high pretherapeutic PET SUV may serve as a simple surrogate for a high absorbed dose and thus, better clinical response 22, several recent studies have found that the median PET SUVmax decreased significantly in tumor lesions with higher absorbed dose 26, 27. Similar results were also reported for PRRT for neuroendocrine tumors 17. In our analysis, the absorbed dose of tumor lesions was presented by the AUCs. In the 177Lu-PSMA-617 group, a highly significant correlation between pretherapeutic PET SUV and their corresponding AUC derived by SPECT/CT was found (r = 0.915 for SUVmax, r = 0.907 for SUVmean). While in the whole-body planar imaging, only moderate correlation between SUV in 68Ga-PSMA-617 PET and the absorbed dose in tumor lesions could be found in 177Lu-PSMA-617 group (r = 0.592 for SUVmax, r = 0.585 for SUVmean). Recent studies reported only moderate correlation (r = 0.44 for SUVmax, r = 0.43 for SUVmean) using 177Lu-PSMA I&T) 28 or no correlation (using 177Lu-PSMA-617) 22 could be found. In these two studies, absorbed dose in tumor lesions was obtained from whole-body planar imaging of 177Lu, which may be insufficient to locate the tumor lesions accurately. Another explanation was that the pretherapeutic imaging PET (PSMA-HBED-CC) and subsequent therapy did not share the same peptide 22, 28. In our correlation analysis, the 177Lu data with CT attenuation correction was used to correlate the 68Ga PET/CT data so the correlation was stronger.

In the 177Lu-EB-PSMA-617 group, the correlation was moderate (r = 0.611 for SUVmax, r = 0.594 for SUVmean), indicating the difference in the intratumoral residence time with and without EB moiety modification. The representative example of biodistribution in Figure 1 and 2 showed that excessive uptake of 177Lu-EB-PSMA-617 in tumor lesions was still obvious at 168 h time point, while that of 177Lu-PSMA-617 already decreased to nearly background level at 24 h p.i. Furthermore, a relatively strong linear relationship between SUV in 68Ga-PSMA-617 PET and 177Lu-PSMA-617 SPECT was seen at 2 h postinjection (R2 = 0.837), while 177Lu-EB-PSMA-617 at 72 h potinjection (R2 = 0.683), indicating slower tumor uptake and longer tumor residence time in 177Lu-EB-PSMA-617. Meanwhile, the linear relationship suggested the best acquisition time point for these two molecules respectively.

There are several limitations of our study. First, in our limited retrospective patient cohort, only one cycle with imaging dose of administered activity was given. Second, a therapy study with more patients is necessary to assess the relationship between pretherapeutic 68Ga PET imaging and 177Lu therapy for candidate selection. Lastly, these mCRPC patients in our study had a very advanced disease stage and received extensive therapy regimens before, which might bring variations to some extent.

CONCLUSIONS

Our initial findings demonstrate that 68Ga-PSMA-617 PET may indicate effective dose in main organs and absorbed dose in tumor lesions both during the 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 treatment, which may help determine appropriate candidates for PRRT. Further investigations with increased 177Lu dose and larger series are warranted to confirm and validate these data.

Acknowledgments

Conflicts of interest and Sources of funding: This work is supported by the National Natural Science Foundation of China (81771874). None declared to all authors.

This work is supported in part by the Key Project on Inter-Governmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (2016YFE0115400), the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), and National Institutes of Health (NIH). This work is also partly supported by the Chinese Academy of Medical Science Major Collaborative Innovation Project (2016-I2M-1–011), Welfare Research Funding for Public Health Professionals (201402001), National Nature Science Foundation (81741142, 81871392) and Beijing Municipal Natural Science Foundation (7161012). None declared to all authors.

REFERENCES

  • 1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. [DOI] [PubMed] [Google Scholar]
  • 2.Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem. 2013;13:951–962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Maffioli L, Florimonte L, Costa DC, et al. New radiopharmaceutical agents for the treatment of castration-resistant prostate cancer. Q J Nucl Med Mol Imaging. 2015;59:420–438. [PubMed] [Google Scholar]
  • 4.Bouchelouche K, Turkbey B, Choyke PL. PSMA PET and Radionuclide Therapy in Prostate Cancer. Semin Nucl Med. 2016;46:522–535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Maurer T, Gschwend J, Rauscher I, et al. Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. J Urol. 2016;195:1436–1443. [DOI] [PubMed] [Google Scholar]
  • 6.Hijazi S, Meller B, Leitsmann C, et al. Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by 68Ga-PSMA-positron emission tomography/computerized tomography. Prostate. 2015;75:1934–1940. [DOI] [PubMed] [Google Scholar]
  • 7.Herlemann A, Wenter V, Kretschmer A, et al. 68Ga-PSMA Positron Emission Tomography/Computed Tomography Provides Accurate Staging of Lymph Node Regions Prior to Lymph Node Dissection in Patients with Prostate Cancer. Eur Urol. 2016;70:553–557. [DOI] [PubMed] [Google Scholar]
  • 8.Pyka T, Okamoto S, Dahlbender M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–2121. [DOI] [PubMed] [Google Scholar]
  • 9.Freitag MT, Radtke JP, Hadaschik BA, et al. Comparison of hybrid (68)Ga-PSMA PET/MRI and (68)Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:70–83. [DOI] [PubMed] [Google Scholar]
  • 10.Kabasakal L, AbuQbeitah M, Aygün A, et al. Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:1976–1983. [DOI] [PubMed] [Google Scholar]
  • 11.Rahbar K, Bode A, Weckesser M, et al. Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer. Clin Nucl Med. 2016;41:522–528. [DOI] [PubMed] [Google Scholar]
  • 12.Baum R, Kulkarni H, Schuchardt C, et al. 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy. J Nucl Med. 2016;57:1006–1013. [DOI] [PubMed] [Google Scholar]
  • 13.Rahbar K, Ahmadzadehfar H, Kratochwil C, et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med. 2017;58:85–90. [DOI] [PubMed] [Google Scholar]
  • 14.Bouchelouche K, Choyke P. Prostate-specific membrane antigen positron emission tomography in prostate cancer: a step toward personalized medicine. Curr Opin Oncol. 2016;28:216–221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Wang Z, Tian R, Niu G, et al. Single Low-Dose Injection of Evans Blue Modified PSMA-617 Radioligand Therapy Eliminates Prostate-Specific Membrane Antigen Positive Tumors. Bioconjug Chem. 2018;29:3213–3221. [DOI] [PubMed] [Google Scholar]
  • 16.Zang J, Fan X, Wang H, et al. First-in-human study of (177)Lu-EB-PSMA-617 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Ezziddin S, Lohmar J, Yong-Hing CJ, et al. Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose of 177Lu octreotate? Clin Nucl Med. 2012;37:e141–147. [DOI] [PubMed] [Google Scholar]
  • 18.Cremonesi M, Botta F, Di Dia A, et al. Dosimetry for treatment with radiolabelled somatostatin analogues. A review. Q J Nucl Med Mol Imaging. 2010;54:37–51. [PubMed] [Google Scholar]
  • 19.Lassmann M, Chiesa C, Flux G, et al. EANM Dosimetry Committee guidance document: good practice of clinical dosimetry reporting. Eur J Nucl Med Mol Imaging. 2011;38:192–200. [DOI] [PubMed] [Google Scholar]
  • 20.Roivainen A, Kahkonen E, Luoto P, et al. Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86–7548 in healthy men. J Nucl Med. 2013;54:867–872. [DOI] [PubMed] [Google Scholar]
  • 21.Wang Z, Zhang M, Wang L, et al. Prospective Study of (68)Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients. Theranostics. 2015;5:882–889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Scarpa L, Buxbaum S, Kendler D, et al. The (68)Ga/(177)Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates. Eur J Nucl Med Mol Imaging. 2017;44:788–800. [DOI] [PubMed] [Google Scholar]
  • 23.Kratochwil C, Giesel FL, Stefanova M, et al. PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617. J Nucl Med. 2016;57:1170–1176. [DOI] [PubMed] [Google Scholar]
  • 24.Delker A, Fendler WP, Kratochwil C, et al. Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:42–51. [DOI] [PubMed] [Google Scholar]
  • 25.Hohberg M, Eschner W, Schmidt M, et al. Lacrimal Glands May Represent Organs at Risk for Radionuclide Therapy of Prostate Cancer with [(177)Lu]DKFZ-PSMA-617. Mol Imaging Biol. 2016;18:437–445. [DOI] [PubMed] [Google Scholar]
  • 26.Baum RP, Kulkarni HR, Schuchardt C, et al. 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy. J Nucl Med. 2016;57:1006–1013. [DOI] [PubMed] [Google Scholar]
  • 27.Kratochwil C, Giesel FL, Leotta K, et al. PMPA for nephroprotection in PSMA-targeted radionuclide therapy of prostate cancer. J Nucl Med. 2015;56:293–298. [DOI] [PubMed] [Google Scholar]
  • 28.Okamoto S, Thieme A, Allmann J, et al. Radiation Dosimetry for (177)Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions. J Nucl Med. 2017;58:445–450. [DOI] [PubMed] [Google Scholar]

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