scholarly journals 177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 263
Author(s):  
Amanda Kristiansson ◽  
Anders Örbom ◽  
Jonas Ahlstedt ◽  
Helena Karlsson ◽  
Wahed Zedan ◽  
...  
Keyword(s):  
Kidney Function ◽  
Single Photon ◽  
Photon Emission ◽  
Absorbed Dose ◽  
Therapeutic Index ◽  
Radical Scavenger ◽  
Emission Computed Tomography ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Plasma Urea

Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3–4 days and 3–4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.

scholarly journals Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 428
Author(s):  
Friederike Völter ◽  
Lena Mittlmeier ◽  
Astrid Gosewisch ◽  
Julia Brosch-Lenz ◽  
Franz Josef Gildehaus ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Biochemical Response ◽  
Emission Computed Tomography ◽  
Radioligand Therapy ◽  
Index Lesion ◽  
Recist 1.1 ◽  
Psma Pet

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

scholarly journals EANM dosimetry committee series on standard operational procedures: a unified methodology for 99mTc-MAA pre- and 90Y peri-therapy dosimetry in liver radioembolization with 90Y microspheres

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Carlo Chiesa ◽  
Katarina Sjogreen-Gleisner ◽  
Stephan Walrand ◽  
Lidia Strigari ◽  
Glenn Flux ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Single Photon ◽  
Photon Emission ◽  
Absorbed Dose ◽  
Calibration Method ◽  
Emission Computed Tomography ◽  
Pet Ct ◽  
Improve Calculation ◽  
Voxel Dosimetry ◽  
Lung Shunt

AbstractThe aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in 90Y microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient–relative calibration method for activity quantification.The identity of 99mTc albumin macro-aggregates (MAA) and 90Y microsphere biodistribution is also assumed. The large observed discrepancies in some patients between 99mTc-MAA predictions and actual 90Y microsphere distributions for lesions is discussed. Absorbed dose predictions to whole non-tumoural liver are considered more reliable and the basic predictors of toxicity. Treatment planning based on mean absorbed dose delivered to the whole non-tumoural liver is advised, except in super-selective treatments.Given the potential mismatch between MAA simulation and actual therapy, absorbed doses should be calculated both pre- and post-therapy. Distinct evaluation between target tumours and non-tumoural tissue, including lungs in cases of lung shunt, are vital for proper optimization of therapy. Dosimetry should be performed first according to a mean absorbed dose approach, with an optional, but important, voxel level evaluation. Fully corrected 99mTc-MAA Single Photon Emission Computed Tomography (SPECT)/computed tomography (CT) and 90Y TOF PET/CT are regarded as optimal acquisition methodologies, but, for institutes where SPECT/CT is not available, non-attenuation corrected 99mTc-MAA SPECT may be used. This offers better planning quality than non dosimetric methods such as Body Surface Area (BSA) or mono-compartmental dosimetry. Quantitative 90Y bremsstrahlung SPECT can be used if dedicated correction methods are available.The proposed methodology is feasible with standard camera software and a spreadsheet. Available commercial or free software can help facilitate the process and improve calculation time.

scholarly journals S VALUES FOR NEUROIMAGING PROCEDURES ON KOREAN PEDIATRIC AND ADULT HEAD COMPUTATIONAL PHANTOMS

2019 ◽  
Vol 185 (2) ◽  
pp. 168-175 ◽  
Author(s):  
Daphnée Villoing ◽  
Ae-Kyoung Lee ◽  
Hyung-do Choi ◽  
Choonsik Lee
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Vitreous Body ◽  
Absorbed Dose ◽  
Emission Computed Tomography ◽  
Dose Calculations ◽  
Positron Emission ◽  
Adult Head ◽  
Computational Phantoms ◽  
Photon Emission Computed Tomography

Abstract Over the past decades, the application of single-photon emission computed tomography and positron emission tomography in neuroimaging has markedly increased. In the current study, we used a series of Korean computational head phantoms with detailed cranial structures for 6-, 9-, 12-, 15-y-old children and adult and a Monte Carlo transport code, MCNPX, to calculate age-dependent specific absorbed fraction (SAF) for mono-energetic electrons ranging from 0.01 to 4 MeV and S values for seven radionuclides widely used in nuclear medicine neuroimaging for the combination of ten source and target regions. Compared to the adult phantom, the 6-y phantom showed up to 1.7-fold greater SAF (cerebellum < cerebellum) and up to 1.4-fold greater S values (vitreous body < lens) for 123I. The electron SAF data, combined with our previous photon SAF data, will facilitate absorbed dose calculations for various cranial structures in patients undergoing neuroimaging procedures.

Dosimetry of 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer: A sub-study of the VISION trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS265-TPS265 ◽  
Author(s):  
Jens Kurth ◽  
Ken Herrmann ◽  
Matthias Eiber ◽  
Kambiz Rahbar ◽  
Martin Heuschkel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Photon ◽  
Photon Emission ◽  
Calibration Procedure ◽  
Whole Body ◽  
Treatment Modalities ◽  
Emission Computed Tomography ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Absorbed Doses

TPS265 Background: Prostate-specific membrane antigen-617 labelled with lutetium-177 (177Lu-PSMA-617) is a promising treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) after treatment with taxane chemotherapy and a novel androgen axis inhibitor. The radiotherapeutic molecule has high PSMA binding affinity, prolonged tumor retention with a rapid kidney clearance, and high tumor-to-background ratio, delivering therapeutically relevant doses of radiation to prostate cancer lesions. A randomized, prospective phase 3 trial to assess the efficacy of 177Lu-PSMA-617 in patients with progressive PSMA-positive mCRPC is ongoing (VISION trial, NCT03511664). However, as with other targeted radionuclide treatment modalities, there may be a risk of radiotoxicity to normal organs. Therefore, estimation of absorbed doses in these organs in a representative manner within the framework of such a study is essential. Methods: As a substudy of the VISION trial, extensive intratherapeutic dosimetry will be performed in a group of 30 patients at four participating German sites. Patients will undergo planar whole-body scintigraphy scans and single-photon emission computed tomography/computerized tomography (SPECT/CT) scans of the upper and lower abdomen at approximately 2, 24, and 48 hours, and 7 days after administration, along with blood sampling and urine collection. SPECT/CT data will be quantitatively reconstructed and a standardized calibration procedure of the imaging and measurement equipment used (SPECT/CT, dose calibrator, well counter) will be performed at all sites according to European Association of Nuclear Medicine (EANM) and Medical International Radiation Dose (MIRD) guidelines [1]. Organ masses will be measured for each patient using CT imaging, if accessible. Absorbed doses for kidneys, liver, spleen, salivary and lacrimal glands, and bone marrow, as well as prostate cancer lesions, will be calculated for each patient following international guidelines [2,3]. References: [1] Ljungberg M et al. J Nucl Med 2016;57:151–62. [2] Siegel JA et al. J Nucl Med 1999;40:37S–61S. [3] Hindorf C et al. Eur J Nucl Med Mol Imaging 2010;37:1238–50. Clinical trial information: NCT03511664.

scholarly journals Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 182
Author(s):  
Ayman Abouzayed ◽  
Sara S. Rinne ◽  
Hamideh Sabahnoo ◽  
Jens Sörensen ◽  
Vladimir Chernov ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Computed Tomography ◽  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Absorbed Dose ◽  
Single Step ◽  
Emission Computed Tomography

Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.

scholarly journals Radionuclide, magnetic resonance and computed tomography imaging in European round back slugs (Arionidae) and leopard slugs (Limacidae)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicola Beindorff ◽  
Fabian Schmitz-Peiffer ◽  
Daniel Messroghli ◽  
Winfried Brenner ◽  
Janet F. Eary
Keyword(s):  
Computed Tomography ◽  
Magnetic Resonance ◽  
Kidney Function ◽  
Single Photon ◽  
Photon Emission ◽  
Functional Anatomy ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Whole Body Imaging ◽  
Imaging Protocol

AbstractOther than in animal models of human disease, little functional imaging has been performed in most of the animal world. The aim of this study was to explore the functional anatomy of the European round back slug (Arionidae) and leopard slug (Limacidae) and to establish an imaging protocol for comparative species study. Radionuclide images with single photon emission computed tomography (SPECT) and positron emission tomography (PET) were obtained after injections of standard clinical radiopharmaceuticals 99mtechnetium dicarboxypropane diphosphonate (bone scintigraphy), 99mtechnetium mercaptoacetyltriglycine (kidney function), 99mtechnetium diethylenetriaminepentaacetic acid (kidney function), 99mtechnetium pertechnetate (mediated by the sodium-iodide symporter), 99mtechnetium sestamibi (cardiac scintigraphy) or 18F-fluoro-deoxyglucose (glucose metabolism) in combination with magnetic resonance imaging (MRI) and computed tomography (CT) for uptake anatomic definition. Images were compared with anatomic drawings for the Arionidae species. Additionally, organ uptake data was determined for a description of slug functional anatomy in comparison to human tracer biodistribution patterns identifying the heart, the open circulatory anatomy, calcified shell remnant, renal structure (nephridium), liver (digestive gland) and intestine. The results show the detailed functional anatomy of Arionidae and Limacidae, and describe an in vivo whole-body imaging procedure for invertebrate species.

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