作者: Wall, Jonathan S ; Williams, Angela D ; Foster, James S ; Lands, Ronald ; Heidel, R Eric ; Richey, Tina ; Powell, Dustin ; Guthrie, Spencer ; Ramchandren, Radhakrishnan ; Kennel, Stephen J ; Whittle, Bryan ; Martin, Emily B ; Stuckey, Alan

BACKGROUNDThe noninvasive detection of cardiac amyloid, as well as deposits in other vital organs, is critical for early diagnosis and quantitative disease monitoring. Positron emission tomography is an intrinsically quantitative imaging modality suitable for high-resolution amyloid detection.OBJECTIVESThis study sought to evaluate the safety and efficacy of a novel amyloid-reactive peptide, designated p5+14, labeled with iodine-124 (¹²⁴I), in patients with diverse types of systemic amyloidosis.METHODSIn a single-site, open label phase 1/2 study (NCT03678259), the safety, biodistribution, and sensitivity of a single intravenous infusion of ¹²⁴I-evuzamitide was assessed in patients with systemic amyloidosis (n = 50), asymptomatic transthyretin sequence variant carriers (n = 2), and healthy volunteers (n = 5). Subjects were administered 1.4 ± 0.2 mg of ¹²⁴I-evuzamitide (71.5 ± 12.4 MBq) and positron emission tomography/x-ray computed tomography images acquired at 5.2 hours (Q25-Q75: 4.9-5.4 hours) postinfusion. Images were assessed visually and semi-quantitatively for positive uptake of radiotracer in the heart and other major organs.RESULTSUptake of ¹²⁴I-evuzamitide in the heart and other abdominothoracic organs was consistent with the patient's clinical presentation and the type of amyloidosis. The patient- and cardiac-associated sensitivity for imaging and clinical observations was 93.6% (95% CI: 82.8%-97.8%) and 96.2% (95% CI: 81.8%-99.8%), respectively. Semi-quantitative uptake of the radiotracer correlated significantly with serum N-terminal pro-B-type natriuretic peptide measurements in patients with light chain-associated amyloidosis. Cardiac uptake was not observed in any healthy volunteers. The agent was well tolerated, with 1 drug-related adverse event and no deaths.CONCLUSIONS¹²⁴I-evuzamitide is an amyloid-binding radiotracer capable of detecting cardiac amyloid in patients with high sensitivity.

2023-06-01·Journal of Nuclear Medicine

Efficacy and Safety of¹²⁴I-MIBG Dosimetry-Guided High-Activity¹³¹I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma

Article

作者: Schmitz, Jochen ; Unger, Nicole ; Schaarschmidt, Benedikt M ; Herrmann, Ken ; Weber, Manuel ; Maric, Ines ; Jentzen, Walter ; Bockisch, Andreas ; Fendler, Wolfgang P ; Prochnow, Andre ; Rischpler, Christoph ; Poeppel, Thorsten D

We aim to evaluate the efficacy and safety of ¹²⁴I-metaiodobenzylguanidine (MIBG) dosimetry-guided high-activity ¹³¹I-MIBG therapy of advanced pheochromocytoma or neuroblastoma. Methods: Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9-69 y, underwent ¹²⁴I-MIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic, and renal function. Response was evaluated by RECIST, International Society of Pediatric Oncology Europe Neuroblastoma-like score, change in PET uptake, and quantitative PET parameters (SUV_max, SUV_peak, metabolic tumor volume, total lesion glycolysis), as well as visual decrease in number or in visual intensity of lesions on baseline to follow-up ¹²⁴I-MIBG PET/CT. Results: The average therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 mo (95% CI), and median progression-free survival was 25 mo (95% CI). Four (29%) and 5 (36%) patients demonstrated response (complete response or partial response) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 mo after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. Conclusion: ¹²⁴I-MIBG dosimetry-guided high-activity ¹³¹I-MIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of ¹²⁴I-MIBG-guided activity escalation should further be assessed in a prospective setting.

2022-07-04·Molecular Pharmaceutics

¹²⁴I Radiolabeled Basiliximab for CD25-Targeted Immuno-PET Imaging of Activated T Cells

Article

作者: Zhu, Hua ; Wang, Shuailiang ; Guo, Qian ; Wen, Li ; Yang, Zhi ; Wang, Pei ; Wang, Zilei ; Liu, Futao

Activated T cells played critical roles in immunotherapy and adoptive T cell therapy, and a non-invasive imaging strategy can provide us useful information concerning the transportation, accumulation, and homing of T cells in vivo. In this paper, by utilizing the long half-life radionuclide iodine-124 (¹²⁴I) and CD25 specific monoclonal antibody Basiliximab, we have fabricated a novel probe, namely, ¹²⁴I-Basiliximab, which was highly promising in the immuno-PET imaging of T cells. In vitro, ¹²⁴I-Basiliximab had superior affinity to CD25 protein (Kd = 5.31 nM) and exhibited much higher accumulation in CD25 high-expression lymphoma cell line Karpas299 than that in CD25-negative cell line Daudi. In vivo, ¹²⁴I-Basiliximab was excreted slowly from the body of mice, rendering it a relatively high effective dose (0.393 mSv/MBq) when applied in the immuno-PET imaging. In Karpas299 tumor xenograft, ¹²⁴I-Basiliximab probe was observed to accumulate in the tumor quickly after tracer administration, with the optimal image acquired at 24 h post-injection. More importantly, PHA-activated hPBMC had much higher uptake of ¹²⁴I-Basiliximab, indicating the potential utility of ¹²⁴I-Basiliximab to discriminate activated hPBMC from its non-activated status. In summary, ¹²⁴I-Basiliximab was fabricated for the first time, which can be applied in CD25-targeted immuno-PET imaging of activated T cells in vivo.

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