Tc-99m labeled small-molecule inhibitors of prostate-specific membrane antigen (PSMA): New molecular imaging probes to detect metastatic prostate adenocarcinoma (PC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 173-173 ◽  
Author(s):  
Joseph Osborne ◽  
Naveed Hassan Akhtar ◽  
Shankar Vallabhajosula ◽  
Anastasia Nikolopoulou ◽  
Kevin P. Maresca ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Post Injection ◽  
Parotid Glands ◽  
Therapeutic Implications

173 Background: Sensitive and specific imaging remains a clinically-relevant problem for men with PC. PSMA is a well established target for imaging of PC with therapeutic implications. We have recently developed novel 99mTc-labeled small molecule inhibitors of the enzymatic domain of PSMA based on glutamate-urea-glutamate and glutamate-urea-lysine pharmacophores, and contain a bis-imidazole chelator to complex Tc-99m. Preclinical studies with PSMA positive LNCaP cells and xenografts demonstrate that 99mTc-MIP-1404 and 99mTc-MIP-1405 bind to PSMA with high affinity and localize in tumors rapidly. This study reports the first human data in men with metastatic PC and in healthy male subjects. Methods: Under an exploratory IND, using a cross-over design, the pharmacokinetics, biodistribution, and tumor uptake of 99mTc-MIP-1404 and 99mTc-MIP-1405 were compared in 6 healthy men and 6 men with radiographic evidence of metastatic PC. Whole body images were obtained at 10 min, 1, 2, 4 and 24 hr. Single photon emission computed tomography (SPECT) was performed between 3–4 hours post injection. Results: Both agents cleared the blood rapidly with MIP-1404 demonstrating significantly lower urinary activity (7%) compared to MIP-1405 (26%). Both agents showed persistent uptake in the salivary, lacrimal and parotid glands. Uptake in liver and kidney was acceptable for imaging at 1-2 hr post injection (PI). In men with PCa, both agents rapidly localized in bone and lymph node lesions as early as 1 hr PI. SPECT demonstrated excellent lesion contrast. Good correlation was seen with bone and CT scans, In majority of patients, more lesions including sub-cm lymph nodes were seen with 99mTc-MIP-1404 and 99mTc-MIP-1405. The high contrast images exhibited signal:noise ratios from 3:1 to 28:1 at 4 and 24 hr. Conclusions: 99mTc-MIP-1404 and 99mTc-MIP-1405 identified a greater number of lesions than bone scans and rapidly detected soft tissue PC lesions including sub-cm lymph nodes. Since 99mTc-MIP-1404 has minimal activity in the bladder, further work is planned to correlate imaging findings with histopathology in patients with high risk clinically-localized PC.

scholarly journals Synthesis and Evaluation of 99mTc-Tricabonyl Labeled Isonitrile Conjugates for Prostate-Specific Membrane Antigen (PSMA) Image

Inorganics ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Nadeem Ahmed Lodhi ◽  
Ji Yong Park ◽  
Kyuwan Kim ◽  
Mi Kyung Hong ◽  
Young Joo Kim ◽  
...  
Keyword(s):  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Prostate Specific Membrane Antigen ◽  
Post Injection ◽  
Tumor Uptake ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA) is a biomarker expressed on the surface of prostate cancer (PCa). In an effort to improve the detection and treatment of PCa, small urea-based PSMA inhibitors have been studied extensively. In the present study, we aimed to develop 99mTc-tricabonyl labeled urea-based PSMA conjugates containing isonitrile (CN-R)-coordinating ligands ([99mTc]Tc-15 and [99mTc]Tc-16). Both the PSMA conjugates were obtained at high radiochemical efficiency (≥98.5%). High in vitro binding affinity was observed for [99mTc]Tc-15 and [99mTc]Tc-16 (Kd = 5.5 and 0.2 nM, respectively) in PSMA-expressing 22Rv1 cells. Tumor xenografts were conducted using 22Rv1 cells and rapid accumulation of [99mTc]Tc-16 (1.87 ± 0.11% ID/g) was observed at 1 h post-injection, which subsequently increased to (2.83 ± 0.26% ID/g) at 4 h post-injection. However, [99mTc]Tc-15 showed moderate tumor uptake (1.48 ± 0.18% ID/g), which decreased at 4 h post-injection (0.81 ± 0.09% ID/g). [99mTc]Tc-16 was excreted from non-targeted tissues with high tumor-to-blood (17:1) and tumor-to-muscle ratio (41:1) at 4 h post-injection at approximately 4 times higher levels than [99mTc]Tc-15. Uptakes of [99mTc]Tc-15 and [99mTc]Tc-16 to PSMA-expressing tumor and tissues were significantly blocked by co-injection of 2-(Phosphonomethyl)-pentandioic acid (2-PMPA), suggesting that their uptakes are mediated by PSMA specifically. Whole-body single photon emission computed tomography imaging of [99mTc]Tc-16 verified the ex vivo biodistribution results and demonstrated clear visualization of tumors and tissues expressing PSMA compared to [99mTc]Tc-15. In conclusion, using [99mTc]Tc-16 rather than [99mTc]Tc-15 may be the preferable because of its relatively high tumor uptake and retention.

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 Tc-99m HYNIC-TOC scintigraphy in dedifferentiated thyroid cancer

2019 ◽  
Vol 12 (4) ◽  
pp. e227910
Author(s):  
Kanhaiyalal Agrawal ◽  
P Sai Sradha Patro ◽  
C Preetam
Keyword(s):  
Thyroid Cancer ◽  
Single Photon ◽  
Somatostatin Receptor ◽  
Photon Emission ◽  
Peptide Receptor Radionuclide Therapy ◽  
Ct Imaging ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Serum Thyroglobulin ◽  
Pet Ct

There is literature evidence showing utility of somatostatin receptor (SSTR) positron emission tomography-CT (PET-CT) imaging in differentiated thyroid cancer with Thyroglobulin Elevated and Negative Iodine Scan (TENIS). These patients are less benefited with I-131 therapy and surgery remains only curable option if disease could be localised. If surgery is not feasible, other therapeutic options are not promising. However, if these patients show strongly positive SSTR imaging, then possibility of peptide receptor radionuclide therapy may be explored. As SSTR PET-CT imaging is expensive and not widely available, Technetium-99m (Tc-99m) hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC), which is a Single photon emission computed tomography (SPECT) tracer, can be used. We are documenting a case of raised serum thyroglobulin antibody and negative I-131 whole body scan with disease recurrence localised on Tc-99m HYNIC-TOC scan.

scholarly journals The value of single-photon emission computed tomography combined with computed tomography imaging in ¹²³I-Metaiodobenzylguanidine scintigraphy in children with neuroblastoma

2021 ◽  
Vol 20 (4) ◽  
pp. 22-32
Author(s):  
E. D. Kireeva ◽  
. Kailash ◽  
T. V. Shamanskaya ◽  
M. Ya. Yadgarov ◽  
D. Yu. Kachanov ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Planar Imaging ◽  
Single Photon Emission ◽  
Emission Computed ◽  
Single Photon Emission Computed ◽  
Photon Emission Computed Tomography

The value of single-photon emission computed tomography combined with computed tomography imaging in ¹²³I-Metaiodobenzylguanidine scintigraphy in children with neuroblastomaWhole body scintigraphy with ¹²³I-Metaiodobenzylguanidine (¹²³I-MIBG) is an important imaging modality for evaluation of patients with neuroblastoma (NB). As the intrinsic nuclear scintigraphic characteristics, the assessment of conventional planar ¹²³I-MIBG images presents some difficulties. The limited resolution of planar images can induce false-negative results for small lesions, whereas the presence of physiologic MIBG uptake is not always easily differentiable from pathologic uptake and can induce false-positive results. Single-photon emission computed tomography combined with computed tomography (SPECT/ CT) hybrid imaging technique, allowing the direct fusion of morphologic and functional information, has been suggested to be more accurate. However, SPECT/CT imaging renders slightly more radiation to patients from CT portion of the study and is time consuming. The aim of our study was to investigate how much SPECT/CT can have additional diagnostic value over planar imaging in NB patients at initial staging. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. A total of 251 SPECT/CT scans following by planar ¹²³I-MIBG imaging scans performed in 251 patients with NB were retrospectively analyzed. In 72.1% of the studies, the whole-body planar images and SPECT/CT images showed the same result. In 27.9% of studies, however, SPECT/CT images provided additional very important information. In our study, the diagnosis reached by planar imaging was revised or specified by SPECT/CT in 70 of the 251 patients and was clinically significant. 

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.

Nuclear Medicine Applications in Pediatric Musculoskeletal Diseases: The Added Value of Hybrid Imaging

2018 ◽  
Vol 22 (01) ◽  
pp. 025-045 ◽  
Author(s):  
Ramesh Iyer ◽  
A. Stanescu ◽  
Marguerite Parisi
Keyword(s):  
Computed Tomography ◽  
Nuclear Medicine ◽  
Single Photon ◽  
Musculoskeletal Diseases ◽  
Photon Emission ◽  
Added Value ◽  
Whole Body ◽  
Response Monitoring ◽  
Emission Computed Tomography ◽  
Nuclear Medicine Procedures

AbstractThe introduction of diphosphonates in the 1970s revolutionized not only nuclear medicine but musculoskeletal imaging as well, providing functional assessment of entities such as osteomyelitis, trauma, and osseous metastatic disease. Although rarely the first-line imaging modality used today, nuclear medicine procedures continue to play a pivotal role in the evaluation of musculoskeletal diseases in children, providing whole-body assessment of disease involvement. More recently, the introduction of technologies such as single-photon emission computed tomography/computed tomography (SPECT/CT), as well as newer positron-emitting tracers such as 18fluorine-fluorodeoxyglucose and sodium 18F-fluorine, particularly when combined with CT (positron emission tomography/CT), have injected new life into the older established techniques and expanded the application of nuclear medicine imaging into new arenas. This article discusses the utility of standard nuclear medicine procedures as they apply to children with musculoskeletal disorders, focusing on the added value of and indications for SPECT/CT. Subsequently, we discuss the expanding role of positron-emitting agents in infection, trauma, and for the diagnosis, staging, and therapeutic response monitoring of children with malignant bone and soft tissue tumors. Differences between disease processes encountered in children as compared with adults are discussed; developmental variants that can, but should not, be confused with disease are illustrated. The need for pediatric-specific protocols is addressed.

scholarly journals Nuclear Medicine Imaging in Neuroblastoma: Current Status and New Developments

2021 ◽  
Vol 11 (4) ◽  
pp. 270
Author(s):  
Atia Samim ◽  
Godelieve A.M. Tytgat ◽  
Gitta Bleeker ◽  
Sylvia T.M. Wenker ◽  
Kristell L.S. Chatalic ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Nuclear Medicine ◽  
Single Photon ◽  
Photon Emission ◽  
Treatment Strategies ◽  
Whole Body ◽  
Current Status ◽  
Emission Computed Tomography ◽  
Nuclear Medicine Imaging ◽  
Disease Extent

Neuroblastoma is the most common extracranial solid malignancy in children. At diagnosis, approximately 50% of patients present with metastatic disease. These patients are at high risk for refractory or recurrent disease, which conveys a very poor prognosis. During the past decades, nuclear medicine has been essential for the staging and response assessment of neuroblastoma. Currently, the standard nuclear imaging technique is meta-[123I]iodobenzylguanidine ([123I]mIBG) whole-body scintigraphy, usually combined with single-photon emission computed tomography with computed tomography (SPECT-CT). Nevertheless, 10% of neuroblastomas are mIBG non-avid and [123I]mIBG imaging has relatively low spatial resolution, resulting in limited sensitivity for smaller lesions. More accurate methods to assess full disease extent are needed in order to optimize treatment strategies. Advances in nuclear medicine have led to the introduction of radiotracers compatible for positron emission tomography (PET) imaging in neuroblastoma, such as [124I]mIBG, [18F]mFBG, [18F]FDG, [68Ga]Ga-DOTA peptides, [18F]F-DOPA, and [11C]mHED. PET has multiple advantages over SPECT, including a superior resolution and whole-body tomographic range. This article reviews the use, characteristics, diagnostic accuracy, advantages, and limitations of current and new tracers for nuclear medicine imaging in neuroblastoma.

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