68Ga-FAPI-46 PET for imaging of gastrointestinal cancers: A prospective interventional single-arm clinical trial (FAPI-PET-GI)

Prior treatment

• Prior external beam radiation therapy (EBRT) within 1 month of enrolment to tumour lesions intended for surgery or biopsy
• Prior chemotherapy, immunotherapy, biologic or targeted oncologic therapy within 1 month prior 68Ga-FAPI-46 PET
• Women of child bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study, unless they are using highly effective methods of contraception during the interventional period. Highly effective contraception methods include: • True sexual abstinence: defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception.• Vasectomised partner is a highly effective birth control method if the partner is the sole sexual partner of the study participant and the vasectomised partner has received medical assessment of the surgical success. • Bilateral tubal occlusion. • Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: - oral - intravaginal - transdermal• Progestogen-only hormonal contraception associated with inhibition of ovulation: - oral - injectable - implantable • Placement of an intrauterine device or intrauterine hormone-releasing system

Other illness

• Known or expected hypersensitivity to 68Ga-68-FAPI-46 or any of the relevant excipients
• History of disease or condition that may critically interfere with participation in this study at the discretion of the investigators

Lab values

• QTcF >470 msec for females and QTcF >450 msec for males on screening ECG or history of congenital long QT syndrome
• Post-menopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms), or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40mIU/mL or have had surgical bilateral oophorectomy or bilateral salpingectomy or hysterectomy or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential

Other

• Participant cannot give consent for the study
• Sexually active males must use a condom during intercourse during the interventional period. A condom is required to be used also by vasectomized men in order to prevent delivery of the study compound via seminal fluid
• Participant can not lie flat or tolerate 68Ga-FAPI-46 PET imaging
• Unwillingness or inability to comply with study and follow-up procedures
• Pregnant, lactating, or breast-feeding women

• Proven or suspected gastrointestinal cancers including: - Hepatocellular carcinoma - Cholangiocarcinoma - Gastric cancer - Pancreatic cancer - Colorectal cancer - Oesophageal cancer
• At initial staging or re-staging of disease
• At least one detectable tumour lesion with any diameter > 1cm
• Intended or performed surgery of biopsy of tumor within 8 weeks before or 8 weeks after enrollment and participants consent to utilise biopsy/tumour specimen for immunohistochemical analysis of FAP expression
• Age ≥ 18 years
• Participant Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Women of child bearing potential (WOCBP), defines as all women physiologically capable of becoming pregnant, can only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test within 24 hours before radiopharmaceutical application