Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NYM005 and initial experience in clear cell renal cell carcinoma: an interim analysis of a prospective trial.

PURPOSE: This first-in-human study aimed to evaluate the radiation dosimetry and whole-body biodistribution of [18F]AlF-NYM005, a novel small-molecule carbonic anhydrase IX (CAIX) targeting agent, and to investigate its ability to detect CAIX-positive tumors using PET scans in a cohort of clear cell renal cell carcinoma (ccRCC) patients.

METHODS

[18F]AlF-NYM005 was synthesized using a fully automatic cassette module Mortenon M1 (Nuoyu, China). Thirty-five patients with a suspicious lesion considered primary renal malignancy or a history of ccRCC were prospectively recruited and studied. All patients underwent [18F]AlF-NYM005 PET/CT examinations and the maximum standardized uptake value (SUVmax) was measured on conventional [18F]AlF-NYM005 PET/CT images. Among these patients, five patients underwent dynamic [18F]AlF-NYM005 PET/CT scanning (120 min) of the lower abdomen. Another subset of five ccRCC patients underwent sequential whole-body PET scans at 30, 60, 90, and 120 min (one of the five patients underwent additional 150 min and 180 min scans) after [18F]AlF-NYM005 injection to assess biodistribution and dosimetry. The influx constant (Ki) was calculated from the dynamic [18F]AlF-NYM005 PET/CT data using the Patlak model. Whole-body biodistribution was calculated as time-activity curves (TACs) describing dynamic uptake patterns in the patients' major organs, followed by calculation of tracer kinetics and cumulative organ activity. Effective doses of [18F]AlF-NYM005 and individual organ doses were also calculated.

RESULTS

[18F]AlF-NYM005 was successfully synthesized with a radiochemical purity of > 95% and an average labeling yield of 36.5 ± 8.3%. All patients tolerated the PET examinations well, and no adverse side effects were observed. The total body effective dose was 7.6E-03 mSv/MBq. The highest agent uptake was observed in the kidneys, stomach, and liver, contributing to an effective dose of 0.0126 ± 0.0029 mSv/MBq. The TACs showed optimal normal organ uptake with high tumor uptake and long retention of up to 2 h post-injection. Notably, a rapid increase of the tracer followed by a rapid decrease in the blood pool, kidney, liver, and tumor lesions was observed, indicating that [18F]AlF-NYM005 was rapidly eliminated from blood and urine. For the kinetic data analysis, the Ki for the primary kidney lesions had a mean of 0.082 ± 0.057 ml/g/min. The CAIX-positive tumors displayed rapid uptake, and all lesions were detectable within 30 min, with no additional lesions observed in the subsequent multi-time point scans. The patient-level sensitivity, specificity, and accuracy of [18F]AlF-NYM005 PET/CT were 93.8%, 75.0%, and 90% for group 1 and 92.3%, 100%, and 93.3% for group 2, respectively. For per-lymph node analysis, [18F]AlF-NYM005 PET/CT demonstrated 92.9% sensitivity, 90.5% specificity, and 91.8% accuracy in diagnosing metastatic lymph nodes. For per-distant metastasis analysis, it showed 90.5% sensitivity, 91.3% specificity, and 90.6% accuracy. The SUVmax of [18F]AlF-NYM005 PET/CT for primary ccRCC lesions was 15.5 ± 7.35. Tumor uptake was positive correlated with immunohistochemical staining findings.

CONCLUSION

This pilot study in ccRCC patients has demonstrated the safety, acceptable radiation dosimetry, favorable biodistribution, and exceptional tumor uptake of [18F]AlF-NYM005. The preliminary diagnostic study indicated the potential utility of [18F]AlF-NYM005 PET/CT, showing promising results in the diagnosis of primary or metastatic ccRCC.

TRIAL REGISTRATION: This study was registered at ClinicalTrial.gov (ChiCTR2200058108) as NYPILOT on 29 March, 2022.