Single Microdose Trial- CXCR4 PET Tracer - Pharmacokinetics and Pharmacodynamics of [68Ga]Ga-R54, a Radiopharmaceutical Directed Toward CXCR4 in Patients With Advanced Solid Neoplasia.

The present study aims to evaluate the pharmacokinetic/pharmacodynamic profile and the engagement capacity of a new PET probe that binds the CXCR4 receptor. A Microdose-Trial (Guideline ICH M3(R2) CPMP/ICH/286/95 type 1 approach and EMEA/CHMP/SWP/28367/07 Rev. 1) is proposed in order to evaluate the pharmacokinetics and pharmacodynamics of a single microdose of the radiopharmaceutical [68Ga]Ga-R54 in patients suffering from solid tumors in the advanced stage of the disease or multiple myeloma. At least 5 and no more than 10 consenting patients with advanced solid tumors (breast, lung, colon, ovary, and pancreas) or multiple myeloma will be recruited with at least 1 patient per pathology whose neoplasm expresses CXCR4. Study patients will receive i.v. a single dose of [68Ga]Ga-R54 ≤100 μg. The localization of the target will be carried out with PET/CT method. Pharmacokinetics will be analyzed by blood samples taken at 2, 5, 10, 30 minutes, 1, 2 and 4 hours post infusion. Patients will be enrolled at least 7 days apart to monitor the onset of adverse events.

Inclusion criteria

• Patients > 18 years
• Patients with histological diagnosis of solid neoplasm (breast, lung, colon, ovary, pancreas) in advanced stages or multiple myeloma evaluated by PET/CT with [18F]FDG carried out in the 3 months prior to enrollment. The neoplasm must express the CXCR4 receptor by immunohistochemistry
• Patients with ECOG performance status 0-2, able to undergo the scheduled diagnostic procedure (PET/CT with [68Ga]Ga-R54).
• Patients with alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase <3 x upper limit of reference range and total bilirubin <2.0 mg/dL
• Patients with creatinine < 1.5 x upper limit of reference range or 24-hour creatinine clearance > 50 mL/min
• Negative serum pregnancy test (b-hCG) for women of childbearing age before administration of [68Ga]Ga-R54).
• Signature of informed consent indicating that the patient (or legal representative) has been informed of all aspects pertinent to the study
• Willingness and ability to comply with scheduled visits, laboratory tests and other study procedures.

Exclusion criteria

• Presence of active infections (e.g. requiring antibiotic therapy) or other serious concomitant illness, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study
• Declared chronic active hepatitis (hepatitis B / C)
• Declared active autoimmune diseases
• Recovery from major trauma including surgery within 4 weeks of study enrollment
• Presence of neurodegenerative diseases
• Pregnancy and/or breastfeeding
• Any conditions that in the opinion of the investigator could hinder compliance with the study protocol
• Patients who have not signed consent to participate in the study