Safety and Diagnostic Performance of 111In-TJD-31 SPECT Imaging in Patients With Solid Tumors

A Single-Arm, Open-Label, Exploratory Clinical Study to Evaluate the Safety, Biodistribution, Dosimetry, and Preliminary Diagnostic Performance of a Novel SPECT Tracer 111In-TJD-31 in Patients With Solid Tumors

This study aims to evaluate the performance of a novel SPECT imaging agent, 111In-TJD-31, which targets placental alkaline phosphatase (ALPP). ALPP is a protein found on the surface of many malignant solid tumor cells but rarely present in healthy adult tissues. The purpose of this study is to assess the ability of 111In-TJD-31 to detect tumor lesions in patients with malignant solid tumors, as well as to evaluate its safety, biodistribution, pharmacokinetics, and radiation dosimetry.

The study will enroll 8 participants: 2 healthy volunteers and 6 patients with confirmed malignant solid tumors. Healthy volunteers will provide blood samples at multiple time points after a single intravenous injection of 111In-TJD-31 to help measure how the agent moves through the body. Patients with malignant solid tumors will receive a single intravenous injection of 111In-TJD-31 and undergo SPECT/CT imaging at several time points post-injection. Participants will be followed for safety assessments through Day 7 after injection.

This is an open-label, exploratory study conducted at Zhongnan Hospital of Wuhan University, with support from Tuo Jiding (Jiaxing) Pharmaceutical Technology Co., Ltd.

Background and Rationale Malignant tumors remain a leading cause of mortality worldwide. Receptor-ligand-based radionuclide molecular imaging plays an increasingly important role in oncological diagnosis and therapy. Placental alkaline phosphatase (ALPP) is a classic "oncofetal antigen" with strict tissue specificity. It is highly expressed in placental trophoblasts during pregnancy but is virtually absent in most healthy adult tissues. Many studies have shown that ALPP is overexpressed in various malignant solid tumors, including germ cell tumors, ovarian cancer, endometrial cancer, and subsets of lung and gastrointestinal cancers. Its dense distribution on tumor cell membranes combined with low background in normal tissues provides a high target-to-noise ratio, making ALPP a promising target for molecular imaging and therapy.

Molecular Characteristics of TJD-31 TJD-31 is a fully humanized IgG1 monoclonal antibody probe developed to specifically target ALPP. It exhibits picomolar affinity (EC50 = 0.012 nM), excellent homologous specificity with no cross-reactivity to other alkaline phosphatase isoforms, rapid receptor-mediated endocytosis (over 80% internalization within 3 hours), and robust physicochemical stability under harsh conditions, supporting reliable radiolabeling and clinical application.

Study Objectives Primary Objective: To evaluate the lesion detection efficacy of 111In-TJD-31 SPECT/CT imaging in patients with malignant solid tumors.

Secondary Objectives: To characterize the safety, biodistribution, and radiation dosimetry of 111In-TJD-31 in patients.

Exploratory Objective: To explore pharmacokinetic characteristics in healthy volunteers.

Study Design This is an exploratory, prospective, open-label clinical study conducted at the Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University. A total of 8 participants will be enrolled sequentially: 2 healthy volunteers and 6 patients with histologically confirmed malignant solid tumors.

Key Inclusion Criteria (for patients):

Voluntary written informed consent before any study-specific procedures; Clinically highly suspected or histologically/cytologically confirmed malignant solid tumors with measurable lesions (target lesions), including treatment-naïve and relapsed patients; Age ≥18 and ≤75 years, male or female; ECOG performance status 0 or 1. Imaging Protocol for Patients Patients will receive a single intravenous dose of 111In-TJD-31 (3-5 mCi). Whole-body planar SPECT/CT imaging will be performed at 4 ± 1 hours, 24 ± 2 hours, and 48 ± 2 hours post-injection, with tomographic imaging of the head/neck, torso, and known tumor lesions.

Pharmacokinetic Protocol for Healthy Volunteers Healthy volunteers will receive a single intravenous dose of approximately 2 mCi. Blood samples will be collected at 0.5, 1, 4, 8, 24, and 48 hours post-injection.

Safety Follow-up All participants will return for a safety visit on Day 7 (±1 day) post-injection, including vital signs, laboratory tests, and electrocardiography. Adverse events and serious adverse events will be recorded from injection through the follow-up period. Healthy volunteers will complete the study after the Day 7 assessment if no further monitoring is required.

The study has been approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University.

Inclusion Criteria:

• For Patients with Solid Tumors:

  1. Voluntary signed written informed consent before any study-specific procedures;
  2. Clinically highly suspected or histologically (or cytologically) confirmed malignant solid tumors with measurable lesions (target lesions), including treatment-naïve and relapsed patients;
  3. Age ≥18 and ≤75 years, male or female;
  4. ECOG performance status 0 or 1;
  5. Life expectancy ≥6 months;
  6. Women of childbearing potential must have a negative pregnancy test, and all participants (including male participants) must agree to use effective contraception during the study period and for at least 3 months after study drug administration.

For Healthy Volunteers:

1. Chinese healthy volunteers, male or female;
2. Age 18 to 55 years (inclusive);
3. Body weight: females 45-80 kg (inclusive), males 50-80 kg (inclusive);
4. Women of childbearing potential must have a negative pregnancy test, and all participants (including male participants) must agree to use effective contraception during the study period and for at least 3 months after study drug administration;
5. Ability to communicate well with the investigator, understand and comply with all study requirements, and voluntarily sign informed consent before any study-related procedures.

Exclusion Criteria:

• For Patients with Solid Tumors:

  1. Pregnant or breastfeeding women, or women planning to become pregnant during the study period or within 3 months after study drug administration (except those who have been postmenopausal for at least 1 year or have undergone surgical sterilization such as bilateral tubal ligation without reversal, bilateral oophorectomy, or hysterectomy); or participants planning to donate sperm or eggs during the study period or within 3 months after study drug administration;
  2. Known or suspected allergy to the study drug or any of its components;
  3. Receipt of another investigational agent at enrollment, or within 5 half-lives or 30 days after the last dose of such agent, whichever is longer;
  4. Use of any radiotherapeutic agent within 90 days prior to study drug administration, or use of any radionuclide diagnostic agent within 3 days prior to study drug administration;
  5. Significant hepatic or renal dysfunction: serum total bilirubin >1.5 × upper limit of normal (ULN), or AST and/or ALT >2.5 × ULN, or serum creatinine >1.5 × ULN;
  6. Active infection at screening;
  7. Unable to lie flat and still for at least 30 minutes during SPECT imaging, or having claustrophobia or other conditions that preclude SPECT imaging;
  8. Any other condition that, in the investigator's opinion, makes the participant unsuitable for the study.

For Healthy Volunteers:

1. Pregnant or breastfeeding women, or women planning to become pregnant during the study period or within 3 months after study drug administration (except those who have been postmenopausal for at least 1 year or have undergone surgical sterilization such as bilateral tubal ligation without reversal, bilateral oophorectomy, or hysterectomy); or participants planning to donate sperm or eggs during the study period or within 3 months after study drug administration;
2. Known or suspected allergy to the study drug or any of its components;
3. Receipt of another investigational agent at enrollment, or within 5 half-lives or 30 days after the last dose of such agent, whichever is longer;
4. Clinically significant abnormalities in hematology, blood biochemistry, or urinalysis at screening;
5. History of any clinically significant disease (including but not limited to cardiac, hepatic, renal, digestive, biliary, endocrine, cardiovascular, neurological, psychiatric, respiratory, immunological, hematological, hematopoietic, or urinary system disease) within 4 weeks prior to screening, as judged by the investigator;
6. Blood pressure >150/100 mmHg or <90/50 mmHg at screening;
7. Use of any prescription or over-the-counter medication (including herbal medicines, dietary supplements, and vitamins, except for routine continuous vitamin use) within 2 weeks prior to study drug administration, unless judged by the investigator as not affecting the study results;
8. Blood donation or blood loss ≥500 mL within 12 weeks prior to study drug administration;
9. History of any malignant tumor;
10. Unable to lie flat and still for at least 30 minutes during SPECT imaging, or having claustrophobia or other conditions that preclude SPECT imaging;
11. Any other condition that, in the investigator's opinion, makes the volunteer unsuitable for the study.