Initial evaluation of [18F]-FACBC for PET imaging of multiple myeloma

Morath, Volker; Heider, Michael; Mittelhäuser, Markus; Rolbieski, Hannes; Stroh, Jacob; Calais, Jérémie; Eiber, Matthias; Bassermann, Florian

doi:10.1186/s13550-022-00876-0

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…In recent years, different groups have assessed the utility of myeloma-specific agents targeted to myeloma proteins such as CD38 and CXCR4. Metabolic tracers such as 18 F-FACBC ( 28 ) and 11 C-acetate ( 29 ) have also been explored as alternatives to 18 F-FDG. Although promising, the short 20-min radioactive half-life of 11 C makes it a challenging radionuclide for routine use.…”

Section: Discussionmentioning

confidence: 99%

First-in-Humans Evaluation of Safety and Dosimetry of⁶⁴Cu-LLP2A for PET Imaging

Laforest¹,

Ghai

Fraum³

et al. 2022

J Nucl Med

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Background: There remains an unmet need for molecularly targeted imaging agents in multiple myeloma (MM). The integrin, very late antigen-4 (VLA4), is differentially expressed in malignant MM cells as well as in the pathogenic inflammatory microenvironmental cells. [ 64 Cu]Cu-CB-TE1A1P-LLP2A ( 64 Cu-LLP2A) is a VLA4 targeted, high-affinity radiopharmaceutical with promising utility for managing patients diagnosed with MM. Here, we evaluated safety and human radiation dosimetry of 64 Cu-LLP2A for potential use in MM patients.Methods: Single dose [ nat Cu]Cu-LLP2A (Cu-LLP2A) tolerability and toxicity study was performed in CD-1 (Hsd:ICR) male and female mice. 64 Cu-LLP2A was synthesized in accordance with the good manufacturing practice compliant procedures. Three MM and six healthy participants underwent 64 Cu-LLP2A-PET/CT or PET/MR scans up to three time points to help determine tracer biodistribution, pharmacokinetics and radiation dosimetry. Time-activity curves were plotted for each participant. Mean organ absorbed doses and effective doses were calculated using the Organ Level INternal Dose Assessment (OLINDA) software. Tracer bioactivity was evaluated via cell binding assays and metabolites from human blood samples were analyzed with analytical radio-high performance liquid chromatography. When feasible, VLA4 expression was evaluated in the biopsy tissues using 14-color flow cytometry.Results: 150-fold mass excess of the desired imaging dose was tolerated well in male and female CD-1 mice (no observed adverse effect level (NOEL)). Time-activity curves from human imaging data showed rapid tracer clearance from blood via kidneys and bladder. The effective dose of 64 Cu-LLP2A in humans was 0.036 ± 0.006 mSv/MBq, and spleen had the highest organ uptake of 0.142 ± 0.034 mSv/MBq. Among all tissues, the red marrow demonstrated highest residence time. Image quality analysis supports early imaging time (4-5 h post injection of the radiotracer) as optimal. Cell studies showed statistically significant blocking for the tracer produced for all of the human studies (82.42 ± 13.47%). Blood metabolism studies confirmed a stable product peak (> 90%) up to 1 h post-injection of the radiopharmaceutical. No clinical or laboratory adverse events related to 64 Cu-LLP2A were observed in the human participants.Conclusions: 64 Cu-LLP2A exhibited a favorable dosimetry and safety profile for use in humans.

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Section: Discussionmentioning

confidence: 99%

First-in-Humans Evaluation of Safety and Dosimetry of⁶⁴Cu-LLP2A for PET Imaging

Laforest¹,

Ghai

Fraum³

et al. 2022

J Nucl Med

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“…74 Additionally, trans-1-amino-3-[ 18 F]-uoro cyclobutane carboxylic-acid (anti-[ 18 F]-FACBC), a leucine analogue, has been approved for imaging of recurrent prostate cancer (PCa) 75 and is a promising PET imaging agent for multiple myeloma. 76 Building on our previous results and aware of the importance of leucine in cancer biology, we sought to develop an 18 F-labelled leucine radiotracer. Below are some of the key considerations for the development of new PET radiochemical reactions: 14,15,77 Reaction compatibility with micro or nanoscale.…”

Section: Rapid 18 F-uorination For Radiotracer Synthesismentioning

confidence: 99%