Clinical Application of CAIX-Targeted PET Imaging in Tumors
According to the 2020 global cancer statistics, renal carcinoma ranks as the fourteenth most common malignant tumor worldwide. In 2020, there were 431,288 new cases and 179,368 deaths from renal cancer, and both the incidence and mortality rates are projected to continue rising by 2025. Early non-invasive diagnosis of clear cell renal cell carcinoma (ccRCC) is crucial for improving prognosis. Nuclear medicine molecular imaging offers the advantages of real-time, dynamic, and non-invasive detection of lesions throughout the body. However, there is currently a lack of highly efficient and targeted molecular probes for early and accurate diagnosis of this tumor in clinical practice.
The high expression of CAIX plays a central role in the pathogenesis of renal cancer by altering cellular metabolism, inducing angiogenesis, promoting epithelial-mesenchymal transition (EMT), invasion, and metastatic spread. CAIX is highly expressed in 95% of ccRCC cases. In fact, CAIX expression levels have been reported as an independent predictor of survival in advanced ccRCC. Moreover, CAIX expression in normal tissues is limited, primarily restricted to the stomach, the basolateral aspects of proliferating small intestinal crypt epithelial cells, and the gallbladder. Therefore, the differential expression of CAIX between ccRCC tumors and normal tissues highlights its potential as a robust target for nuclear medicine molecular probe research and development in ccRCC.
This study utilized high-throughput screening to identify small molecules with high affinity for CAIX. These molecules were subsequently cyclized and modified to enhance their in vivo stability. A bifunctional chelator, H3RESCA, was introduced at the C-terminus to construct the small-molecule compound RESCA-CAIX-LT. PET probes were prepared by radiolabeling with 68Ga or 18F, and their diagnostic efficacy for renal cancer was investigated. Small-animal PET imaging initially demonstrated that the probe exhibits high affinity and excellent imaging performance. The modifications also altered the in vivo metabolic profile of the original design, reducing non-specific uptake in organs such as the stomach, small intestine, and gallbladder. Furthermore, toxicological experiments confirmed the probe's high safety profile and in vivo stability.
Studieoversikt
Status
Forhold
Studietype
Registrering (Antatt)
Fase
- Tidlig fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Lei Xia
- Telefonnummer: +86 18811177191
- E-post: xialei9012288@126.com
Studiesteder
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Haidian
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Beijing, Haidian, Kina, 10000
- Rekruttering
- Peking University Cancer Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
-Hematological, hepatic, and renal functions meeting the following criteria: Complete Blood Count: WBC ≥4.0×10⁹/L or Neutrophils ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L; Coagulation: PT or APTT ≤1.5 × ULN (Upper Limit of Normal); Hepatic Function: T-Bil ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (or ≤5 × ULN for subjects with liver metastases); ALP ≤2.5 × ULN (or ≤4.5 × ULN for subjects with bone or liver metastases); Renal Function: BUN ≤1.5 × ULN, SCr ≤1.5 × ULN.
Normal cardiac function;
- Expected survival ≥12 weeks;
- Good compliance with follow-up;
- At least one measurable target lesion according to RECIST 1.1 criteria;
- Women of childbearing potential (aged 18-49) must have a negative pregnancy test within 7 days prior to the examination. Male and female patients of childbearing potential must agree to use effective contraception to prevent pregnancy during the study and for 3 months after the examination;
- Patients for whom the clinician recommends a PET/CT examination for tumor diagnosis and staging;
- Patients are fully capable of understanding the study, voluntarily agree to participate, and provide written informed consent.
Exclusion Criteria:
- Severe abnormalities in hepatic, renal, or hematological function;
- Patients planning for pregnancy;
- Pregnant or lactating women;
- Inability to lie flat for 30 minutes;
- Refusal to participate in this clinical study;
- Presence of claustrophobia or other psychiatric disorders;
- Any other condition deemed unsuitable for participation by the investigator.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Diagnostisk
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Renal cancer patients
This is an exploratory study.
Initially, we plan to enroll renal cancer patients or suspected patients scheduled for pathological biopsy or surgical tumor resection within the next 2 months.
Following the collection of preliminary sample data, a further analysis will be conducted to calculate the required sample size.
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68Ga/18F-CAIX-LT-BCH (0.05-0.1 mCi/kg) is intravenously administered, followed immediately by whole-body dynamic imaging using the United Imaging uEXPLORER total-body PET/CT system. If indeterminate lesions are observed on routine imaging, delayed imaging may be performed for further evaluation. The patient is positioned supine and instructed to breathe quietly. The acquired data are reconstructed using the Ordered Subset Expectation Maximization (OSEM) algorithm to generate dynamic PET image frames. Static PET/CT or PET/MRI Protocol: Following intravenous administration of the quality-controlled 68Ga/18F-CAIX-LT-BCH (0.05-0.1 mCi/kg), the patient rests for 50-60 minutes before undergoing whole-body or regional static scanning. The patient is positioned supine and maintains quiet breathing. Image data are reconstructed using the OSEM algorithm to produce dynamic PET image frames. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Standardized Uptake Value (SUV) of target or suspected tumor lesions in malignant tumor subjects for 68Ga/18F-CAIX-LT-BCH across imaging time points
Tidsramme: Immediately after completion of imaging
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Immediately after completion of imaging
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Samarbeidspartnere og etterforskere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 2025YJZ37
Plan for individuelle deltakerdata (IPD)
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