Diagnostic accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting osteomalacia-associated tumors

Li, Bo; Duan, Lili; Li, Xiali; Shi, Jingqi; Li, Huiqiang; Liu, Huimin; Cheng, Xiaoliang; Wang, Xinyu; Gao, Yongju

doi:10.3389/fonc.2023.1228575

Cited by 3 publications

(2 citation statements)

References 33 publications

(100 reference statements)

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“…Most often chelators, e.g. HYNIC and MAG3, are employed in clinic to prepare 99m Tc-labeled radiopharmaceuticals ( 59 – 63 ). Nevertheless, several compounds in clinical studies ( 64 – 66 ), including sdAbs (NCT 04483167, NCT 04040686) ( 67 – 69 ), make use of 99m Tc-tricarbonyl chemistry, showing the potential of this strategy for clinical translation.…”

Section: Discussionmentioning

confidence: 99%

The GEM-handle as convenient labeling strategy for bimodal single-domain antibody-based tracers carrying 99mTc and a near-infrared fluorescent dye for intra-operative decision-making

Declerck,

Huygen,

Mateusiak

et al. 2023

Front. Immunol.

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Intra-operative fluorescence imaging has demonstrated its ability to improve tumor lesion identification. However, the limited tissue penetration of the fluorescent signals hinders the detection of deep-lying or occult lesions. Integrating fluorescence imaging with SPECT and/or intra-operative gamma-probing synergistically combines the deep tissue penetration of gamma rays for tumor localization with the precision of fluorescence imaging for precise tumor resection. In this study, we detail the use of a genetically encoded multifunctional handle, henceforth referred to as a GEM-handle, for the development of fluorescent/radioactive bimodal single-domain antibody (sdAb)-based tracers. A sdAb that targets the urokinase plasminogen activator receptor (uPAR) was engineered to carry a GEM-handle containing a carboxy-terminal hexahistidine-tag and cysteine-tag. A two-step labeling strategy was optimized and applied to site-specifically label IRDye800CW and 99mTc to the sdAb. Bimodal labeling of the sdAbs proved straightforward and successful. 99mTc activity was however restricted to 18.5 MBq per nmol fluorescently-labeled sdAb to prevent radiobleaching of IRDye800CW without impeding SPECT/CT imaging. Subsequently, the in vivo biodistribution and tumor-targeting capacity of the bimodal tracer were evaluated in uPAR-positive tumor-bearing mice using SPECT/CT and fluorescence imaging. The bimodal sdAb showed expected renal background signals due to tracer clearance, along with slightly elevated non-specific liver signals. Four hours post-injection, both SPECT/CT and fluorescent images achieved satisfactory tumor uptake and contrast, with significantly higher values observed for the anti-uPAR bimodal sdAb compared to a control non-targeting sdAb. In conclusion, the GEM-handle is a convenient method for designing and producing bimodal sdAb-based tracers with adequate in vivo characteristics.

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Section: Discussionmentioning

confidence: 99%

The GEM-handle as convenient labeling strategy for bimodal single-domain antibody-based tracers carrying 99mTc and a near-infrared fluorescent dye for intra-operative decision-making

Declerck,

Huygen,

Mateusiak

et al. 2023

Front. Immunol.

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“…[ 99m Tc]Tc-HYNIC-ALUG was synthesized using previously described procedures ( 14 , 17 ). The radiochemical purity of the [ 99m Tc]Tc-HYNIC-ALUG produced was greater than 95%, as determined by high-performance liquid chromatography (HPLC).…”

Section: Methodsmentioning

confidence: 99%

[99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of 227 consecutive patients with newly diagnosed prostate cancer: a 5-year monocentric retrospective study

Li,

Ding,

Duan

et al. 2024

Front. Endocrinol.

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PurposeThe purpose of this study was to assess the effectiveness of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of patients with newly diagnosed PCa.MethodsA retrospective analysis was conducted on 227 consecutive patients who underwent [99mTc]Tc-HYNIC-ALUG SPECT/CT imaging for the primary staging of newly diagnosed PCa. The presence and location of PSMA-positive lesions were determined, and the maximum standardized uptake values (SUVmax) of the primary prostate tumor were also measured. The metastatic findings and SUVmax were stratified according to International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) levels, and D’Amico classification. Furthermore, the [99mTc]Tc-HYNIC-ALUG SPECT/CT findings were compared to the histopathological findings in patients who had undergone radical prostatectomy with pelvic lymph node dissection (PLND).ResultsOf the 227 patients, 92.1% (209/227) had positive [99mTc]Tc-HYNIC-ALUG SPECT/CT findings. Advanced disease was detected in 38.8% (88/227) of the patients and was positively correlated with increasing ISUP grade and PSA levels. Lymph node metastases (both pelvic and extrapelvic), bone metastases, and visceral metastases were detected in 30.0% (68/227), 25.6% (58/227), and 3.1% (7/227) of the patients, respectively. For the 129 patients who underwent radical prostatectomy with PLND, the sensitivity of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the evaluation of PCa was 90.7% (117/129). The sensitivity, specificity, accuracy, and positive and negative predictive values for detecting pelvic lymph node metastases on [99mTc]Tc-HYNIC-ALUG SPECT/CT were 23.5% (12/51), 93.6% (73/78), 65.9% (85/129), 70.6% (12/17), and 65.2% (73/112), respectively. Among the 209 patients with PSMA-avid primary prostate disease, the SUVmax of the primary prostate tumor was significantly associated with ISUP grade (p<0.0001), PSA levels (p<0.0001), D’Amico classification (p<0.0001), and advanced disease (p<0.0001). Receiver operating characteristic (ROC) analysis revealed that a PSA level >19.8 ng/ml and SUVmax of the primary prostate tumor >7.4 had a sensitivity of 71.6% and 71.6% and specificity of 76.9% and 82.6%, respectively, for detecting metastatic disease.Conclusions[99mTc]Tc-HYNIC-ALUG SPECT/CT emerges as a valuable imaging tool for the initial staging of newly diagnosed PCa. The presence of advanced disease and the SUVmax of the primary prostate tumor were positively correlated with ISUP grade and PSA levels.

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Optimization Processes of Clinical Chelation-Based Radiopharmaceuticals for Pathway-Directed Targeted Radionuclide Therapy in Oncology

Tomiyoshi,

Wilson,

Mourtada

et al. 2024

Pharmaceutics

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Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT, 68Ga and 99mTc are the current standards for diagnostic radionuclides, while 177Lu and 225Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to 225Ac daughters 221Fr and 213Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose–response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses.

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Diagnostic accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting osteomalacia-associated tumors

Cited by 3 publications

References 33 publications

The GEM-handle as convenient labeling strategy for bimodal single-domain antibody-based tracers carrying 99mTc and a near-infrared fluorescent dye for intra-operative decision-making

The GEM-handle as convenient labeling strategy for bimodal single-domain antibody-based tracers carrying 99mTc and a near-infrared fluorescent dye for intra-operative decision-making

[99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of 227 consecutive patients with newly diagnosed prostate cancer: a 5-year monocentric retrospective study

Optimization Processes of Clinical Chelation-Based Radiopharmaceuticals for Pathway-Directed Targeted Radionuclide Therapy in Oncology

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