New Results

Radiolabeling of PSMA-617 with 89Zr: A Novel Use of DMSO for Radiochemical Yield Enhancement and Preliminary Small-Animal PET Results

Ryota Imura, Atsuko Nakanishi Ozeki, Nanako Shida, Mika Kobayashi, Hiroyuki Ida, Youichiro Wada, Nobuyoshi Akimitsu, Yoshitaka Kumakura
doi: https://doi.org/10.1101/2021.06.28.450175

Abstract

Introduction Prostate-specific membrane antigen (PSMA)-targeted ligands, including PSMA-617, have been developed for theranostics of prostate cancer. 68Ga-PSMA-617 is the de facto standard of PSMA Positron Emission Tomography (PET) for imaging in prostate cancer patients prior to radioligand therapy (RLT) with 177Lu-PSMA-617. The dose-limiting toxicity for PSMA-RLT is damage to the kidney. PET scans using 68Ga-PSMA-617 have to be performed within a few hours of injection due to its short half-life (68 min). However, the presence of radioactivity in urine at the PET imaging timepoint hampers the dose optimization of 177Lu (half-life 6.6 d)-labeled PSMA-617. Thus, the long-lived positron emitter 89Zr (half-life 3.3 d) is suited for optimizing the doses of 177Lu-PSMA-617 because PET scans can be performed after excretion of radioactive urine. Although 89Zr has great potential for PET imaging, its inadequate incorporation into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), limits its applications. Here, we report the radiolabeling of PSMA-617 with 89Zr and preliminary PET imaging studies using 89Zr-PSMA-617.

Methods DMSO and HEPES buffer were used to label PSMA-617 with 89Zr. The dissociation constant (Kd) of 89Zr-PSMA-617 was determined using a cell-binding assay. Delayed-PET scans using 89Zr-PSMA-617 were performed at 24 h (N = 5).

Results 89Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The Kd value was 6.8 nM. In PET imaging, standardized uptake value (SUV) was highest in LNCaP tumors (SUVmax = 0.98 ± 0.32), whereas it was low in kidney (SUVmax = 0.18 ± 0.7).

Conclusion The preparation of 89Zr-PSMA-617 was achieved by using the DMSO and HEPES buffer. 89Zr-PSMA-617 visualize the PSMA positive LNCaP tumors without accumulation in bladder.

Advances in knowledge and implications for patient care The use of 89Zr-PSMA-617 to predict the radiation doses in normal tissues lead to safe and effective RLT with 177Lu-PSMA-617.

1 Introduction

Prostate-specific membrane antigen (PSMA) is a transmembrane protein of 750 amino acids that is expressed in the prostate; some modest expression of PSMA is seen in normal tissues including the kidneys, salivary glands and lacrimal glands [1,2]. PSMA is overexpressed in prostate malignancy [3] and its expression is highest in metastatic castration-resistant prostate cancers (mCRPCs) that have a high Gleason score, which is indicative of an aggressive tumor. Thus, ligands that bind to PSMA-expressing cancer cells allow the targeted delivery of diagnostic and therapeutic agents [4–6]. One such small molecular ligand, PSMA-617, has potential utility in providing PSMA-targeted radioligand therapy (RLT) to patients with mCRPC [2,7]. PSMA-617 contains 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), as a metal chelating moiety. PSMA-617 is most frequently conjugated to 68Ga and 177Lu as positron and beta ray-emitting radionuclides, respectively [2,8]. Thus, 68Ga-PSMA-617 is a de facto standard in PSMA PET for mCRPC, before RLT with 177Lu-PSMA-617.

Radionuclides with short half-lives are preferred for PET imaging because they expose patients to low radiation dose. However, the use of a positron emitter with a long half-life would provide advantages in terms of the ability to predict the radiation doses of normal tissues and organs at later time point. It is advantageous to compare them to the doses that are required to induce toxicity in mCRPC during PSMA-RLT. The dose-limiting toxicity of PSMA-RLT is set by the effects on the kidneys, because proximal renal tubular cells express PSMA. PET scans using 68Ga-PSMA-617 should be performed within a few hours from injection due to the short half-life of 68Ga (68 min). However, radioactivity persists in the urine at this time, which prevents dose optimization of 177Lu-labeled PSMA-617 (half-life 6.6 d). We hypothesized that the long-lived positron emitter 89Zr (half-life 3.3 d) would be better than 68Ga-PSMA-617 for optimizing the doses of 177Lu-PSMA-617, because PET scans could be performed after excretion of the radioactive urine. However, despite this potential advantage, the synthesis of 89Zr-PSMA-617 has not yet been achieved to the best of our knowledge.

Beyond the facilitation of dose optimization, the used of 89Zr offers additional advantages. First, its long half-life is ideal for delayed-PET scans. The tumor contrast against background is improved over time due to the clearing of non-specific radioligand distribution. Thus, PET scans at later time points from the injection (delayed-PET scans) yield high-contrast PET images. Indeed, high-contrast PET images were obtained by scanning patients at least 2–3 h after injection of 68Ga-PSMA-617 [2]. This delay can be extended up to 24 h or later if 89Zr-PSMA-617 is used. For this reason, higher contrast PET images are expected when 89Zr-PSMA-617 is used. Second, the relatively low positron energy of 89Zr (Eβ+: 396 keV, the mean positron range in water: 1.23 mm) improves spatial resolution compared to 68Ga (Eβ+: 836 keV, mean positron range in water: 3.48 mm) [9]. Third, a ready-to-use 89Zr-PSMA-617 formulation could be delivered from a central radiochemical facility; in contrast, 68Ga-labeled PSMA regents must be prepared under the radiochemist’s quality control in each hospital. Therefore, 89Zr-PSMA-617 may enable PSMA-targeted PET imaging even in hospitals that cannot afford to prepare 68Ga-labeled PSMA regents.

In this study, we hypothesized that 89Zr-PSMA-617 would be suited for optimizing the doses of 177Lu-PSMA-617. In what we believe to be the first report of its kind, we describe the radiolabeling of PSMA-617 with 89Zr in a mixture of aqueous buffer and organic solvent. In addition, we report a preliminary PET imaging study using 89Zr-PSMA-617.

2 Materials and methods

2.1 Production and purification of 89Zr

The 89Zr was produced from 89Y (natural abundance 100%) target via (p,n) reactions by a cyclotron (Cyclone 18, IBA). The radionuclide purity of irradiated 89Y targets was analyzed using a high-purity Ge detector (GMX15, Seiko EG&G). The produced 89Zr was purified by modified procedures described by Holland et al. [10]. Irradiated 89Y targets were dissolved in 2 mol/L HCl and loaded into a hydroxamate resin column. The column was washed with 10 mL of 2 mol/L HCl and 10 mL of water before elution of 89Zr with 3 mL of 1 mol/L oxalic acid. The eluate was loaded into Sep-Pak Accell Plus QMA Plus Light Cartridge (Waters). The cartridge was washed sequentially with 50 mL of water, 1 mL of 0.025 mol/L HCl, 1 mL of 0.05 mol/L HCl, and 0.3 mL of 0.1 mol/L HCl. Then, the 89Zr chloride solution was recovered by addition of 0.6 mL of 0.1 mol/L HCl.

The oxalic acid remaining in the purified 89Zr chloride solution was analyzed by quantifying ultraviolet (UV) absorbance at 220 nm using a Biospec Nano UV spectrometer (Shimadzu).

2.2 Radiolabeling of PSMA-617

PSMA-617 was radiolabeled with 89Zr in a mixture of HEPES buffer and organic solvent. Solvent choice was determined by the results of the following experiments. One microliter of 10-2 mol/L PSMA-617 (10 nmol), 449 μL of 0.5 mol/L HEPES buffer (pH 7.0), 500 μL of organic solvent, and 50 μL of 89Zr chloride solution were added to tubes and reacted at 90C for 30 min. Methanol (MeOH), ethanol (EtOH), N, N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and dimethylsulfoxide (DMSO) were tested. Water was also tested as a reference. The oxalate concentration was controlled by adding a volume of 10-2 mol/L oxalic acid to obtain the following final oxalic acid concentrations: 0 mol/L, 10-5 mol/L, 5 × 10-5 mol/L, and 10-6 mol/L. The radiochemical yield (RCY) was evaluated by instant thin-layer chromatography (ITLC) using ITLC-SG (Agilent) and 1 mol/L ammonium acetate/methanol (1:1) as the mobile phase.

89Zr-PSMA-617 for in vivo and in vitro experiments was prepared as follows. One microliter of 10-2 mol/L PSMA-617 (10 nmol), 699 μL of 0.5 mol/L HEPES buffer (pH 7.0), 1,000 μL of DMSO, and 300 μL of 89Zr chloride solution were added to tubes and reacted at 90°C for 30 min. Oxalic acid was not added. The purification was performed using high-performance liquid chromatography (HPLC) with 2 mmol/L acetic acid (solvent A) and methanol (solvent B), and a 5–100% solvent B gradient over 20 min at a flow rate of 1 mL/min. The fractionated 89Zr-PSMA-617 solution was dried in vacuo. Finally, 89Zr-PSMA-617 was redissolved by saline and used for the experiments here described.

2.3 Cell culture

The PSMA-positive (PSMA+) LNCaP cell line (metastatic lesion of human prostatic adenocarcinoma, ATCC CRL-1740) and the PSMA-negative (PSMA-) PC-3 cell line (bone metastasis of a grade IV prostatic adenocarcinoma, ATCC CRL-1435) were cultured in RPMI-1640 medium supplemented with heat-inactivated 10% fetal calf serum. Cell culture was performed at 37°C in a 5% CO2 atmosphere. The cells were harvested using trypsin-ethylenediaminetetraacetic acid (trypsin-EDTA; 0.25% trypsin, 0.02% EDTA). The expression of PSMA protein in each cell line was investigated by western blot using anti-PSMA rabbit antibody (Cell Signaling Technology) [11].

2.4 Cell-based assays

The dissociation constant (Kd) and internalization of 89Zr-PSMA-617 was determined using cell-based assays. Twenty four-well plates seeded with 105 LNCaP cells were used for both assays. The plates were precoated with poly-L-lysine to improve cell adherence [12]; the cells were then grown overnight at 37°C and 5% CO2. Blocking experiments were also conducted for each assay to assess non-specific binding. The medium used in the blocking assay experiments included 2-phosphonomethyl pentanedioic acid (2-PMPA, 200 μmol/L).

The of Kd 89Zr-PSMA-617 was evaluated based on methods reported previously [13].

After removing the supernatant, different concentrations (0.12–500 nmol/L) of 89Zr-PSMA-617 in 500 μL RPMI-1640 medium was added. The well plates were incubated for 30 min at 4°C. The supernatants were then removed and the cells were washed twice with ice-cold PBS followed by the addition of NaOH (0.3 mol/L, 600 μL) to each well. The cell suspensions were transferred to microtubes for measurement in a gamma counter (Hidex). The Kd values were determined by plotting specific-binding (total binding minus non-specific binding) against the molar concentration of the added radioligands followed by nonlinear regression analysis using GraphPad Prism 7 software.

Internalization of 89Zr-PSMA-617 to LNCaP cells was evaluated by methods reported previously [14]. After removing the supernatant, 32 nM of 89Zr-PSMA-617 in 250 μL Opti-MEM was added, and well plates were incubated for 45 min at 37°C. The cells were washed four times with ice-cold PBS and then washed twice with 50 mM glycine (pH 2.8). After washing the cells with PBS, the internalized fraction was determined by lysis of the LNCaP cells using 0.3 M NaOH. The radioactivity collected from the glycine and hydroxide fractions was measured in a gamma counter. The specific cell surface binding and specific internalization were calculated by subtracting the nonspecific cell surface binding and the nonspecific internalized fraction and expressed as %ID/106 LNCaP cells.

2.5 Mouse tumor model

This study was approved by the Animal Experimentation Committee on Isotope Science Center, The University of Tokyo. All animal experiments were carried out according to The University of Tokyo Animal Experimentation Regulations and ARRIVE guidelines.

Seven-week-old male nude mice (BALB/c nu/nu) were purchased from Japan SLC Inc. Mouse tumor models were established by subcutaneously injection both of LNCaP (5 × 106 cells) to the right shoulder and PC-3 (5 × 106 cells) to left shoulder. Each cell line was suspended in 50% Matrigel (Corning) before injection. This mouse tumor model was used for biodistribution and PET imaging studies of 89Zr-PSMA-617.

2.6 PET imaging and biodistribution studies

In order to evaluate whether 89Zr-PSMA-617 can visualize PSMA positive tumors, preliminary small-animal PET imaging studies were performed. 89Zr-PSMA-617 saline solution (~5 nmol per mouse, 3–7 MBq per mouse, N = 5) were injected via a lateral tail vein into mice bearing both LNCaP (right shoulder, PSMA+) and PC-3 (left shoulder, PSMA-) tumor xenografts. The anesthetized animals (2% isoflurane) were promptly placed into the PET scanner (Clairvivo PET, Shimadzu Corporation) to perform a 30 min PET scan at 24 h p.i.

The standardized uptake value (SUV) for PSMA+, PSMA-, and kidney at p.i. 24 h was calculated as SUVmax, SUVmean (95%), and SUVpeak. SUVmax is the SUV of the hottest voxel within a defined volume of interest (VOI). SUVmean (95%) is the SUV for voxels with a signal higher than 95% of the maximum intensity in VOI. SUVpeak is the average SUV computed within a fixed-size VOI containing the hottest pixel value. A sphere around the hottest pixel with a 1.6-mm diameter was set as the fixed-size VOI in this study.

After the PET scans 24 h after injection, the animals were sacrificed and the organs of interest were dissected and weighed. The radioactivity of each organ was measured using a gamma counter (Cobra quantum, PerkinElmer). The mean value and the standard deviation of %ID/g was calculated.

2.7 Statistical analysis

All statistical analyses in this study were conducted using GraphPad Prism 7. The standard deviation was adopted as the error range. For the PET imaging experiments, the difference in the accumulation of 89Zr-PSMA-617 in PSMA+ and PSMA-tumors was assessed using a paired-t-test.

3 Results

3.1 Production and purification of 89Zr

The Ge detector observed only specific γ-ray energies from 89Zr (e.g., 511, 909 keV). An average 69 ± 4% of activity was recovered after 89Zr purification. The oxalic acid content of the purified 89Zr solution was below 10-5 mol/L. These data confirm the high radionuclidic purity and low oxalic acid concentration of the purified 89Zr solution.

3.2 Radiolabeling of PSMA-617

In order to obtain a high radiochemical yield (RCY) of 89Zr-PSMA-617, we set out to identify the optimum reaction buffer. As summarized in Figure 1, RCY was significantly increased by using organic solvent. DMSO had no significant effect on RCY, at any of the oxalate concentrations used. The overall RCY of the 89Zr-PSMA-617 saline solution, including the HPLC separation process, was 70 ± 9%. Our data show that a high RCY of 89Zr-PSMA-617 can be successfully prepared using a mixture of DMSO and HEPES buffers. Quality control of 89Zr-PSMA-617 prepared in this study was performed using radio-HPLC. Chromatographs of non-radioactive PSMA-617, free 89ZrCl4, and 89Zr-PSMA-617 are shown in the Supplementary Material (Figure S1). The retention time of 89Zr-PSMA-617 was consistent with that of PSMA-617.

FIGURE 1.
FIGURE 1.

The radiochemical yield of 89Zr-PSMA-617 reacted in a mixture of HEPES buffer and organic solvent with different oxalate concentrations.

3.3 Cell binding assay

A cell binding assay was performed to determine the Kd of 89Zr-PSMA-617. Western blot experiments confirmed the expression of PSMA protein in LNCaP cells and its absence in PC-3 cells (Figure S2). The binding assay revealed a Kd of 6.8 nM (95% confidence interval: 2.6–17 nM) for 89Zr-PSMA-617 (Figure 2).

FIGURE 2.
FIGURE 2.

A representative graph of experiments performed to determine the Kd values showing counts measured in cell samples exposed to different concentrations of 89Zr-PSMA-617. N=3 for both experiments and error bars indicate the standard deviation.

In LNCaP, the specific cell surface binding of 89Zr-PSMA-617 was 19.17 ± 0.65%ID/106 cells, and the specific internalization was 12.66 ± 0.60%/106 cells.

3.4 PET imaging and biodistribution studies

Delayed-PET imaging experiments using LNCaP (PSMA+) and PC-3 (PSMA-) tumor-bearing mice were performed 24 h after injection. Figure 3 (a) shows an example of maximum intensity projection (MIP) PET/CT images; these images were obtained using the mouse shown in Figure 3 (b). Significant accumulation of activity was found in LNCaP tumors (PSMA+) and kidneys but not in PC-3 tumors (PSMA-). The SUVs of other tissues were all below 0.1. The panels in Figure 3 (c–e) summarize the SUVs for PSMA+ cells, PSMA-cells, and kidney at 24 h p.i. There was a significant difference in SUV between PSMA+ and PSMA-samples (P < 0.01).

FIGURE 3.
FIGURE 3.

PET/CT image of 89Zr-PSMA-617 at 24 h and comparisons of SUV in tumors and kidney. (a) PET/CT image of LNCaP (PSMA+) and PC-3 (PSMA-) tumor-bearing mice at 24 h p.i. (Abbreviations: bl = bladder, ki = kidney.) (b) A picture of the mouse used for PET/CT imaging experiments. (c–e) Comparison of SUV for PSMA+, PSMA-, and kidney at 24 h p.i. N = 5; error bars indicate the standard deviation. SUV was calculated as SUVmax, SUVmean (95%), and SUVpeak. P-values lower than 0.01 are represented by two asterisks (**).

Phantom experiments using NEMA PET Small Animal Phantom imaging device are shown in the Supplementary material (Figure S3).

The distribution profiles of 89Zr-PSMA-617 in LNCaP (PSMA+) and PC-3 (PSMA-) tumor-bearing mice 24 h after injection are shown in Figure 4. The highest accumulation (1.76 ± 0.61%ID/g) was in LNCaP tumors (PSMA+) and the second highest (0.46 ± 0.15%ID/g) was in the kidneys. The accumulation in PC-3 tumors (PSMA-) and other tissues was similar to the background level (below 0.1%ID/g).

FIGURE 4.
FIGURE 4.

Biodistribution of 89Zr-PSMA-617 in LNCaP-(PSMA+) and PC-3 (PSMA-) tumor-bearing mice at 24. h p.i. N = 7; error bars indicate the standard deviation. P-values lower than 0.001 are represented by three asterisks (***).

4 Discussion

Here, we have established a method of 89Zr-PSMA-617 synthesis using an organic solvent. In previous studies, radiolabeling of the DOTA chelator with 89Zr was performed in the presence of HEPES buffer alone [15]. Under this condition, very high concentrations of DOTA (higher than 10-4 mol/L (100 nmol/mL)) were required to obtain a high radiochemical yield (RCY) (> 90%) [16]. Considering that a small mass of PSMA-617 or PSMA-11 (typically 2 nmol) is administered to each patient, such a high DOTA concentration results in low specific radioactivity (SA) [7,17,18]. In contrast, we demonstrate in the current report that 89Zr radiolabeling of PSMA-617 can be achieved with a DOTA concentration of 5 × 10-6 mol/L (5 nmol/mL), which is one-twentieth of the conventional concentration, by using DMSO. Our improved technique effectively reduces the PSMA-617 concentration required for efficient 89Zr radiolabeling to the concentration commonly used for 68Ga radiolabeling (5–50 nmol/mL) [7,14].

We speculate that the irreversible formation of 89Zr hydroxide 89Zr(OH)4 was responsible for the low RCY when organic solvent is not used. Due to the poor aqueous solubility of Zr hydroxide [19], 89Zr would be poorly reactive with DOTA once 89Zr hydroxide is formed. The ability to achieve high RCYs when an organic solvent is used is probably due to inhibition of 89Zr hydroxide formation. Since Zr oxalate is more readily formed than Zr hydroxide [20], a slight amount of oxalate might improve RCY. Indeed, RCY was consistently high when using DMSO, irrespective of the oxalate concentrations tested in this study (Figure 1). DMSO is a solvent frequently used in pharmaceutical synthesis. Although the DMSO concentration in the final formulation needs to be controlled, we suggest that radiolabeling using DMSO would be acceptable in future clinical studies.

The Kd values of 89Zr-PSMA-617 (6.8 nM) agreed with those of PSMA-617 labeled with other radionuclides [13,21–23]. The specific internalization of 89Zr-PSMA-617 (12.66 ± 0.60%/106 cells) was close to 177Lu-PSMA-617 (16.17 ± 3.66%/106 cells). While DOTA-conjugated peptides are usually combined with divalent or trivalent metal ions, 89Zr4+ (tetravalent) labeled DOTA-conjugated peptides also exhibited comparable cell binding ability and internalization.

As we anticipated, PSMA+ lesions could be visualized using delayed-PET imaging with long-lived 89Zr-PSMA-617 while unfavorable accumulation in the bladder was avoided (Figure 4). In contrast, clinical studies show that radioactive 68Ga- and 44Sc-PSMA-617 remain in the bladder at the time of PET-scanning [7,24]. Therefore, we propose that 89Zr-PSMA-617 is a more suitable reagent for the prediction of cytotoxic doses of PSMA-RLT. However, we note that the PET imaging studies of 89Zr-PSMA-617 were performed in animal experiments only, and future clinical studies will be required to validate our hypothesis. In addition, the SA of 89Zr-PSMA-617 prepared in this study was relatively low (~ 1 GBq/μmol) because 89Zr purification was not automated and we were limited in the amount of radioactivity that could be handled due to the radiation safety guidelines of our facility. Thus, a relatively large amount of radioligand (~5 nmol per mouse) was administrated. The accumulation of 89Zr-PSMA-617 (1.76 ± 0.61%ID/g) in tumors was lower than that of 177Lu-PSMA-617 (10.58 ± 4.50%ID/g) [7]. This discrepancy could be attributed to differences in the number of injected radioligands (177Lu-PSMA-617: 0.06 nmol). Research interest in future studies will be the automation of 89Zr purification to the chloride form and comparisons of 89Zr-PSMA-617 and 177Lu-PSMA-617 biodistribution when lower levels are administered (> 1 nmol per mouse).

Delayed-PET imaging at 24 h p.i. have been achieved by 64Cu-PSMA-617. However, the biodistribution profile of 64Cu-PSMA-617 at 24 h p.i. was different to that of 89Zr-PSMA-617. Accumulation of 89Zr-PSMA-617 in the liver was negligible (below 0.1%ID/g), while that of 64Cu-PSMA-617 at 24 h p.i. was considerably higher (9.08%ID/g) [21]. The increased liver uptake of 64Cu-PSMA-617 is most probably due to free radionuclides, because 64Cu-Macrocyclic complexes, which have limited in vivo stability, are dissociated by superoxide dismutase in the liver [25,26]. In contrast, in vivo dissociation of 89Zr-PSMA-617 was inferred to be low. Free 89Zr in plasma accumulates in the bone and liver [27,28]. Our biodistribution experiment revealed negligible accumulation (below 0.1%ID/g) in these organs, which also highlights the biochemical stability of 89Zr-PSMA-617 in vivo. The low accumulation in bone and liver agrees well with the amount of 89Zr-DOTA complex in these organs at 24 h p.i. (bone: 0.036%ID/g, liver: 0.068%ID/g) [15].

Radioactive urine in the bladder can also complicate the evaluation of signals coming from adjacent organs, such as the prostate. Additionally, urine spots in the ureters could be misdiagnosed as lymph node metastases in human PET images of PSMA. These issues cannot be avoided by using PSMA ligands labeled with 18F or 68Ga due to their short half-lives. In contrast, 89Zr-PSMA-617 allows the visualization of PSMA expression in primary prostate lesions, because the long half-life of 89Zr allows scanning to be performed after all radioactive urine has been completely excreted. Thus, the use of 89Zr-PSMA-617 could be extended to the diagnostics of primary lesions. However, it should be kept in mind that PMSA expression is apparently high in patients with benign prostatic hyperplasia (BPH) [29]. Future human studies with 89Zr-PSMA-617 are required to clarify its utility in this context.

5 Conclusion

Herein, we have described the preparation and use of 89Zr-PSMA-617 for PET imaging studies. The preparation of 89Zr-PSMA-617 was achieved in this study for the first time by using the mixture solvent of HEPES buffer and DMSO. 89Zr-PSMA-617 prepared in this study clearly visualize the PSMA positive LNCaP tumors without accumulation in bladder. The relatively long half-life of 89Zr circumvents the problem of unfavorable bladder accumulation, and 89Zr-PSMA-617 could therefore be an optimum choice for pre-therapeutic dosimetry of 177Lu-PSMA-617. For the same reason, 89Zr-PSMA-617 could be used to visualize primary prostate lesions in PC patients who are being evaluated for the presence of metastases. The use of 89Zr-PSMA-617 could also be extended to the diagnostics of primary lesions.

Disclosure

Ryota Imura and Hiroyuki Ida are employees of JFE Engineering Corporation. This research was partially conducted with research funds of the JFE Engineering Corporation.

Acknowledgments

This research was conducted with research funds from JFE Engineering Corporation, which employs two of this paper’s authors (Ryota Imura and Hiroyuki Ida).

We gratefully thank Professor Hiroshi Watabe (Cyclotron and Radioisotope Center, Tohoku University) for supporting the operation of the PET scanner and data analysis. We also thank Toshifumi Omura and Toru Matsumoto (JFE Engineering Corporation) for technical help.

Footnotes

  • Funding This research was conducted with research funds from JFE Engineering Corporation. No other potential conflicts of interest relevant to this article exist.

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Supplementary Material

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Radiolabeling of PSMA-617 with 89Zr: A Novel Use of DMSO for Radiochemical Yield Enhancement and Preliminary Small-Animal PET Results
Ryota Imura, Atsuko Nakanishi Ozeki, Nanako Shida, Mika Kobayashi, Hiroyuki Ida, Youichiro Wada, Nobuyoshi Akimitsu, Yoshitaka Kumakura
bioRxiv 2021.06.28.450175; doi: https://doi.org/10.1101/2021.06.28.450175
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