scholarly journals Evaluation of Radiation dosimetry of 99mTc-HYNIC-PSMA and imaging in prostate cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jianping Zhang ◽  
Jiangang Zhang ◽  
Xiaoping Xu ◽  
Linjun Lu ◽  
Silong Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Dosimetry ◽  
Tumor Imaging ◽  
Absorbed Dose ◽  
Ct Images ◽  
Tracer Uptake ◽  
Whole Body ◽  
Imaging Method ◽  
Absorbed Doses ◽  
Total Body

Abstract This study aims to evaluate the radiation dosimetry of a new technetium-99m‒labelled small-molecule inhibitor of prostate-specific membrane antigen (HYNIC-Glu-Urea-A, 99mTc-HYNIC-PSMA) and its feasibility as a tumor-imaging agent in prostate cancer (PCa) patients. A total of 15 PCa patients were enrolled in this study. For the dosimetry study, 5 PCa patients received whole-body planar scans at 0.5 h, 1 h, 2 h, 4 h and 8 h after 99mTc-HYNIC-PSMA injection. The Dosimetry Toolkit (GE, Milwaukee) was used to process the data and segment the organs in the SPECT/CT images, which were then projected onto planar images. The organ-specific absorbed doses, total-body absorbed doses and 99mTc-HYNIC-PSMA effective doses of patients were calculated using OLINDA/EXM 1.1 software. Whole-body SPECT/CT images were also acquired from additional 10 prostate patients to investigate the feasibility of 99mTc-HYNIC-PSMA for imaging tumors by calculating the ratio of tumor-to-background tracer uptake at 2 h after 740 MBq administration. The total-body absorbed dose was 1.54E-03 ± 2.43E-04 mGy/MBq, and the effective dose was 3.72E-03 ± 4.5E-04 mSv/MBq. Compared to published studies of other similar PSMA tracers and 99mTc-targeted conventional tracers, the absorbed doses of 99mTc-HYNIC-PSMA in all organs showed that it could be used safely in the human body. In addition, 99mTc-HYNIC-PSMA showed high tracer uptake (with a tumor-to-background ratio of 9.42 ± 2.62) in the malignant lesions of PCa patients, making it a promising radiopharmaceutical imaging method for site-specific management of PCa.

scholarly journals Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Bin Kim ◽  
In Ho Song ◽  
Yoo Sung Song ◽  
Byung Chul Lee ◽  
Arun Gupta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Dosimetry ◽  
Xenograft Model ◽  
Absorbed Dose ◽  
Patient Specific ◽  
Internal Radiation ◽  
Washout Phase ◽  
Heterogeneous Tissue ◽  
Organ Level ◽  
Reported Data

Abstract[68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

scholarly journals α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

2021 ◽  
Author(s):  
S. Schumann ◽  
U. Eberlein ◽  
C. Lapa ◽  
J. Müller ◽  
S. Serfling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Patients ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Absorbed Dose ◽  
Peripheral Blood Mononuclear ◽  
Absorbed Doses ◽  
Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

scholarly journals Is nuclear medicine really safe?

2002 ◽  
Vol 45 (spe) ◽  
pp. 115-118
Author(s):  
Nicole Colas-Linhart
Keyword(s):  
Nuclear Medicine ◽  
Human Serum Albumin ◽  
Radiation Dose ◽  
Serum Albumin ◽  
Human Serum ◽  
Absorbed Dose ◽  
Cellular Level ◽  
Whole Body ◽  
Absorbed Doses ◽  
Standard Models

In nuclear medicine, radiation absorbed dose estimates calculated by standard models at the whole body or organ are very low. At cellular level, however, the heterogeneity of radionuclide distributions of radiation dose patterns may be significant. We present here absorbed doses at cellular level and evaluate their possible impact on the usually assumed risk/benefit relationships in nuclear medicine studies. The absorbed dose values calculated are surprisingly high, and are difficult to interpret. In the present study, we show calculated doses at the cellular level and discuss possible biological consequences, for two radiopharmaceuticals labelled with technetium-99m: human serum albumin microspheres used for pulmonary scintigrapies and HMPAO used to labelled leukocytes.

scholarly journals Kezdeti tapasztalatok a 99mTc-PSMA-SPECT/CT-vel prosztatarákos betegekben

2018 ◽  
Vol 159 (35) ◽  
pp. 1433-1440
Author(s):  
István Farkas ◽  
Zsuzsanna Besenyi ◽  
Anikó Maráz ◽  
Zoltán Bajory ◽  
András Palkó ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Bone Scintigraphy ◽  
Transmembrane Protein ◽  
Tracer Uptake ◽  
Whole Body ◽  
Primary Prostate Cancer ◽  
Cancer Tumor ◽  
Visceral Metastases ◽  
Male Patients

Abstract: Introduction: The prostate-specific membrane antigen (PSMA) is a transmembrane protein, that is highly expressed on the surface of prostate cancer cells. In the last few years, several PSMA-specific ligands have been developed, that can be successfully used to detect primary prostate cancer, tumor recurrences and metastases as well. Aim: The goal of our work was to examine the clinical application of a 99mtechnetium-labeled PSMA-radiopharmaceutical as part of the routine diagnostics of prostate cancer. Method: We examined 15 male patients with verified prostate adenocarcinoma with suspicion of progression or recurrence of the disease. We performed whole-body PSMA-SPECT/CTs and multiparametric MRIs of the prostate and the pelvic regions within a week. We used 99mTc-mas3-y-nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were visually evaluated by independent observers. The results were compared with the follow-up bone scintigraphies as well. Results: Twenty-two PSMA-positive lesions were found. Nine of them were localized outside, 13 were within the MRI’s field of view. From these 13 lesions, 7 matched with the SPECT/CT results and in 5 cases the MRI images showed no abnormalities. In one case, bone metastasis was suspected on the MRI scan but there was no corresponding pathological tracer uptake on the SPECT images. In two patients, none of the examinations showed signs of prostate malignancy. Four patients had PSMA-positive bone metastases. One of them had a matching PSMA/SPECT and bone scintigraphy result and in one case the PSMA examination showed metastasis in contrast to the negative bone scintigraphy. Conclusion: PSMA-SPECT/CT with 99mTc-mas3-y-nal-k(Sub-KuE) is a promising diagnostic tool. This technique is capable of visualizing bone metastases and it can detect local recurrences and visceral metastases as well. Orv Hetil. 2018; 159(35): 1433–1440.

64Cu-PSMA-BCH: A New Radiotracer for Delayed PET Imaging of Prostate Cancer

2021 ◽  
Author(s):  
Teli Liu ◽  
Chen Liu ◽  
Zhongyi Zhang ◽  
Ning Zhang ◽  
Xiaoyi Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pet Imaging ◽  
Radiation Dosimetry ◽  
Whole Body ◽  
Post Injection ◽  
Human Organ ◽  
Fine Needle ◽  
Fine Needle Aspirates ◽  
Psma Pet

Abstract PurposeDevelop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. Methods64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. Results64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA (+) 22Rv1 cells than PSMA (-) PC-3 cells (5.59±0.36 and 1.97±0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 h to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 4 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. Conclusion64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.

scholarly journals Is it necessary to reduce the radioiodine dose in patients with thyroid cancer and renal failure?

2010 ◽  
Vol 54 (4) ◽  
pp. 413-418 ◽  
Author(s):  
José Willegaignon ◽  
Verena Pinto Brito Ribeiro ◽  
Marcelo Sapienza ◽  
Carla Ono ◽  
Tomoco Watanabe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Dose Adjustment ◽  
Absorbed Dose ◽  
Whole Body ◽  
Half Time ◽  
Dialysis Therapy ◽  
Absorbed Doses ◽  
131I Activity ◽  
Dosimetric Data ◽  
Higher Doses

The objective of this study were to obtain dosimetric data from a patient with thyroid cancer simultaneously undergoing peritoneal dialysis therapy, so as to determine the appropriate amount of 131I activity to be applied therapeutically. Percentages of radioiodine in the blood and the whole-body were evaluated, and radiation absorbed doses were calculated according to OLINDA/EXM software. Whole-body 131I effective half-time was 45.5 hours, being four times longer than for patients without any renal dysfunction. Bone-marrow absorbed dose was 0.074 mGy/MBq, with ablative procedure maintenance at 3.7 GBq, as the reported absorbed dose was insufficiently restrictive to change the usual amount of radioiodine activity administered for ablation. It was concluded that radioiodine therapeutic-dose adjustment, based on individual patient dosimetry, is an important way of controlling therapy. It also permits the safe and potential delivery of higher doses of radiation to tumors and undesirable tissues, with a minimum of malignant effects on healthy tissues.

scholarly journals First-In-Human Results on the Biodistribution, Pharmacokinetics, and Dosimetry of [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2

2021 ◽  
Vol 14 (12) ◽  
pp. 1212
Author(s):  
Sanjana Ballal ◽  
Madhav Prasad Yadav ◽  
Euy Sung Moon ◽  
Vasko S Kramer ◽  
Frank Roesch ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Gall Bladder ◽  
Oral Mucosa ◽  
Absorbed Dose ◽  
Left Colon ◽  
Whole Body ◽  
Lacrimal Glands ◽  
Right Colon ◽  
Physiological Uptake ◽  
Absorbed Doses

Recently, great interest has been gained regarding fibroblast activation protein (FAP) as an excellent target for theranostics. Several FAP inhibitor molecules such as [68Ga]Ga-labelled FAPI-02, 04, 46, and DOTA.SA.FAPi have been introduced and are highly promising molecular targets from the imaging point of view. FAP inhibitors introduced via bifunctional DOTA and DOTAGA chelators offer the possibility to complex Lutetium-177 due to an additional coordination site, and are suitable for theranostic applications owing to the increased tumor accumulation and prolonged tumor retention time. However, for therapeutic applications, very little has been accomplished, mainly due to residence times of the compounds. In an attempt to develop a promising therapeutic radiopharmaceutical, the present study aimed to evaluate and compare the biodistribution, pharmacokinetics, and dosimetry of [177Lu]Lu-DOTA.SA.FAPi, and [177Lu]Lu-DOTAGA.(SA.FAPi)2 in patients with various cancers. The FAPi agents, [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2, were administered in two different groups of patients. Three patients (mean age—50 years) were treated with a median cumulative activity of 2.96 GBq (IQR: 2.2–3 GBq) [177Lu]Lu-DOTA.SA.FAPi and seven (mean age—51 years) were treated with 1.48 GBq (IQR: 0.6–1.5) of [177Lu]Lu-DOTAGA.(SA.FAPi)2. Patients in both the groups underwent serial imaging whole-body planar and SPECT/CT scans that were acquired between 1 h and 168 h post-injection (p.i.). The residence time and absorbed dose estimate in the source organs and tumor were calculated using OLINDA/EXM 2.2 software. Time versus activity graphs were plotted to determine the effective half-life (Te) in the whole body and lesions for both the radiotracers. Physiological uptake of [177Lu]Lu-DOTA.SA.FAPi was observed in the kidneys, colon, pancreas, liver, gall bladder, oral mucosa, lacrimal glands, and urinary bladder contents. Physiological biodistribution of [177Lu]Lu-DOTAGA.(SA.FAPi)2 involved liver, gall bladder, colon, pancreas, kidneys, and urinary bladder contents, lacrimal glands, oral mucosa, and salivary glands. In the [177Lu]Lu-DOTA.SA.FAPi group, the highest absorbed doses were noted in the kidneys (0.618 ± 0.015 Gy/GBq), followed by the colon (right colon: 0.472 Gy/GBq and left colon: 0.430 Gy/GBq). In the [177Lu]Lu-DOTAGA.(SA.FAPi)2 group, the colon received the highest absorbed dose (right colon: 1.160 Gy/GBq and left colon: 2.870 Gy/GBq), and demonstrated a significantly higher mean absorbed dose than [177Lu]Lu-DOTA.SA.FAPi (p < 0.011). [177Lu]Lu-DOTAGA.(SA.FAPi)2 had significantly longer median whole-body Te compared to that of [177Lu]Lu-DOTA.SA.FAPi [46.2 h (IQR: 38.5–70.1) vs. 23.1 h (IQR: 17.8–31.5); p-0.0167]. The Te of tumor lesions was significantly higher for [177Lu]Lu-DOTAGA.(SA.FAPi)2 compared to [177Lu]Lu-DOTA.SA.FAPi [86.6 h (IQR: 34.3–94.6) vs. 14 h (IQR: 12.8–15.5); p-0.0004]. The median absorbed doses to the lesions were 0.603 (IQR: 0.230–1.810) Gy/GBq and 6.70 (IQR: 3.40–49) Gy/GBq dose per cycle in the [177Lu]Lu-DOTA.SA.FAPi, and [177Lu]Lu-DOTAGA.(SA.FAPi)2 groups, respectively. The first clinical dosimetry study demonstrated significantly higher tumor absorbed doses with [177Lu]Lu-DOTAGA.(SA.FAPi)2 compared to [177Lu]Lu-DOTA.SA.FAPi. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is safe and unveiled new frontiers to treat various end-stage cancer patients with a theranostic approach.

scholarly journals Simplification of Dosimetry in 90Y-Radioembolization Therapy Using Dual Planar Images.

2021 ◽  
Author(s):  
mohammad abuqbeitah ◽  
Özgür Akdağ ◽  
mustafa demir ◽  
sertaç asa ◽  
kerim sönmezoğlu
Keyword(s):  
Scatter Correction ◽  
Absorbed Dose ◽  
Whole Body ◽  
Whole Body Scan ◽  
Body Scan ◽  
Absorbed Doses ◽  
Significant Difference ◽  
Lung Shunt ◽  
The Impact ◽  
Healthy Liver

Abstract Aim: The purpose was to provide practical and effective method for performing 90Y dosimetry with 99mTc-MAA. The impact of scatter and attenuation correction (AC) on the injected 90Y activity and absorbed doses to critical organs was also further target beyond this study.Material and Methods: 18 patients (F: 3, M: 15) were subjected to 90Y therapy. 99mTc-MAA (111-222 MBq) was injected into the targeted liver, followed by a whole-body scan (WBS) with peak-window at 140 keV (15% width), and one down-scatter window. SPECT/CT scan was acquired over the lungs and liver regions. The lung shunt fractions were fashioned from the standard WBS, scatter corrected WBS, only scatter corrected SPECT and SPECT/CT with attenuation and scatter correction. The absorbed doses to tumor and surrounding healthy tissue were estimated with alternative approaches involving AC-SC (SPECT/CT), NoAC-SC (SPECT), NoAC-NoSC+LSF (SC-WBS), AC-SC+LSF (WBS), and NoAC-NoSC+LSF (WBS).Results: The average LSF deviations between the standard LSF and those obtained from AC-SC, NoAC-SC, and SC-WBS was -50% (-29/-71), -32%(-8/-67), and -45%(-13/80), respectively. The prescribed 90Y activity (GBq/Gy) was decreased by a range of 2-11%, 1-9%, and 2-7% with using LSFs from AC-SC, NoAC-SC, SC-WBS images. The absorbed dose to tumour and healthy liver tissue were calculated as 112±90 Gy and 30±18 Gy/GBq by AC-SC (SPECT/CT), 117±108 and 30±22 by NoAC-SC (SPECT), 110±100 and 31±21 Gy/GBq by NoAC-NoSC+LSF (SC-WBS), 106±84 and 28±17 Gy/GBq by AC-SC+LSF (WBS), while the absorbed dose was 90±85 and 28±20 Gy/GBq by using NoAC-NoSC+ LSF (WBS). Overall, no significant difference (p< 0.05) in the tomour and the health liver dose between all the approaches with/and without scatter correction. However, the scatter correction caused a significant difference in the lung shunt fractions (p <0.05).Conclusion: Scatter correction has a significant effect on the lung shunt fractions, planned activity and number of 90Y treatments. However, a minimal or negligible change was occurred on the absorbed dose to tumours and surrounding healthy liver. The good agreement between SPECT/CT approach, and scatter corrected whole-body scan might be practical and effective route for 90Y dosimetry.

Estimation of [177Lu]PSMA-617 tumor uptake based on voxel-wise 3D Monte Carlo tumor dosimetry in patients with metastasized castration resistant prostate cancer

2020 ◽  
Vol 59 (05) ◽  
pp. 365-374
Author(s):  
Theresa Ida Götz ◽  
Elmar Wolfgang Lang ◽  
Olaf Prante ◽  
Michael Cordes ◽  
Torsten Kuwert ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Monte Carlo ◽  
Three Dimensional ◽  
Absorbed Dose ◽  
Whole Body ◽  
Patient Specific ◽  
Average Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Before And After

Abstract Objective Patients with advanced prostate cancer are suitable candidates for [177Lu]PSMA-617 therapy. Integrated SPECT/CT systems have the potential to improve the accuracy of patient-specific tumor dosimetry. We present a novel patient-specific Monte Carlo based voxel-wise dosimetry approach to determine organ and total tumor doses (TTD). Methods 13 patients with histologically confirmed metastasized castration-resistant prostate cancer were treated with a total of 18 cycles of [177Lu]PSMA-617 therapy. In each patient, dosimetry was performed after the first cycle of [177Lu]PSMA-617 therapy. Regions of interest were defined manually on the SPECT/CT images for the kidneys, spleen and all 295 PSMA-positive tumor lesions in the field of view. The absorbed dose to normal organs and to all tumor lesions were calculated by a three dimensional dosimetry method based on Monte Carlo Simulations. Results The average dose values yielded the following results: 2.59 ± 0.63 Gy (1.67–3.92 Gy) for the kidneys, 0.79 ± 0.46 Gy (0.31–1.90 Gy) for the spleen and 11.00 ± 11.97 Gy (1.28–49.10 Gy) for all tracer-positive tumor lesions. A trend towards higher TTD was observed in patients with Gleason Scores > 8 compared to Gleason Scores ≤ 8 and in lymph node metastases compared to bone metastases. A significant correlation was determined between the serum-PSA level before RLT and the TTD (r = –0.57, p < 0.05), as well as between the TTD with the percentage change of serum-PSA levels before and after therapy was observed (r = –0.57, p < 0.05). Patients with higher total tumor volumes of PSMA-positive lesions demonstrated significantly lower kidney average dose values (r = –0.58, p < 0.05). Conclusion The presented novel Monte Carlo based voxel-wise dosimetry calculates a patient specific whole-body dose distribution, thus taking into account individual anatomies and tissue compositions showing promising results for the estimation of radiation doses of normal organs and PSMA-positive tumor lesions.

First-in-human phase 1 PET study of CTT1057, a novel 18F-labeled imaging agent targeting prostate specific membrane antigen (PSMA) in prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16562-e16562
Author(s):  
Rahul Raj Aggarwal ◽  
Spencer Behr ◽  
Youngho Seo ◽  
Kenneth Gao ◽  
Vahid Rahanfar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salivary Gland ◽  
Phase 1 ◽  
Imaging Study ◽  
Preliminary Evidence ◽  
Tracer Uptake ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Comparison Results ◽  
Psma Pet

e16562 Background: Urea-based 68Ga-PSMA PET is increasingly being utilized for diagnostic purposes in prostate cancer; however high tracer uptake within the salivary gland and kidney may be dose-limiting upon translation to radiotherapy. We developed a novel 18F labeled agent, CTT1057, a PSMA inhibitor based on a phosphoramidate scaffold with nanomolar and irreversible binding affinity to PSMA and robust internalization, and performed a first-in-human imaging study. Methods: Patients (pts) with metastatic castration resistant prostate cancer (mCRPC) were eligible. 10 mCi (370 MBq) of CTT1057 was injected and whole body PET/MR imaging (SIGNA PET/MR, GE) was performed 60 min post-injection. SUVmean in normal organs was recorded by drawing a 1 cm3 volume-of-interest. SUVmax was determined for each PSMA-avid metastasis. 10 randomly selected, consecutive 68Ga-PSMA PET scans from an independent cohort were used for descriptive comparison. Results: 5 pts with mCRPC were enrolled, with average age of 66 years (range 35–85) and median PSA of 12.2 (range 0.73 – 157.7). 55 PSMA-avid metastases were seen, including 37 osseous (average SUVmax = 8.1 ± 4.4), 15 lymph node (SUVmax = 11.0 ± 6.1), and 3 pulmonary (SUVmax = 3.2 ± 0.6). 31 (83%) and 12 (32%) of the PSMA-avid osseous lesions were visible on CT and bone scan, respectively. The mean short axis diameter of PSMA-avid lymph nodes was 0.7 ± 0.4 cm. Tumor-to-background ratios (liver, muscle, blood pool) were 2.8 ± 2.3, 14.9 ± 11.6, and 3.2 ± 2.4, respectively. SUVmean in salivary gland and kidney were 3.6 ± 0.4 and 9.1 ± 0.8 for CTT1057 and 15.8 ± 2.7 and 35.9 ± 9.6 for 68Ga-PSMA, respectively. No tracer-related adverse events were observed and radiation dose estimates for organs and whole-body effective dose were within acceptable limits. Conclusions: 18F-labeled CTT1057 targeting PSMA, detected mCRPC lesions in the soft tissue and bone at greater sensitivity than conventional imaging. CTT1057 distribution of uptake was similar to urea-based PSMA imaging, with preliminary evidence of lower uptake in the salivary gland and kidney. Further clinical studies of the CTT1057 backbone as a diagnostic and therapeutic agent in mCRPC are warranted. Clinical trial information: NCT02916537.

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