Imaging of Viral Thymidine Kinase Activity in EBV-Associated and KSHV-Associated Malignancies
Johns Hopkins Kimmel Cancer Center in Baltimore
Primary endpoint: 1.In EBV-associated or KSHV-associated malignancies, evaluate the potential for enzymatic targeting as evidenced by the ability to image 124I-FIAU tracer uptake in tumor at baseline and following chemotherapy or biologic therapy with agents that may induce viral TK activation. Secondary endpoints: 1.Describe the frequency of tumor targeting according to type of treatment and histology. 2.Describe the kinetics of radiolabeled FIAU by estimating radiation exposure to tumor and normal tissues that could be delivered with therapeutic radiopharmaceuticals after EBV-TK activation. 3.Define standardized uptake values that correlate with tumor visualization on FIAU-PET. 4.Describe changes in viral DNA in plasma as a function of chemotherapy and the association with imaging by FIAU-PET.
Inclusion Criteria: - Age 18 years or older. - EBV-positive or KSHV-associated malignancy, including but not limited to: a. EBV+ Hodgkin lymphoma b. EBV+ non-Hodgkin lymphoma or lymphoproliferative disease c. Primary effusion lymphoma d. Kaposi?s sarcoma e. EBV+ gastric cancer f. EBV+ nasopharyngeal cancer - Measurable disease (at least one lesion on radiographic or exam assessment measuring greater than 2 cm in longest axis). - ECOG performance status of 0, 1, or 2. - Patients must be able to lie flat for at least 60 minutes and fit on PET/CT. - In patients who agree to post-therapy imaging with FIAU-PET, planned treatment with standard agents or investigational agents that can potentially activate herpesvirus TK, including but not limited to: a. Platinum compounds (for example, cisplatin, carboplatin) b. Anthracyclines (for example, doxorubicin or pegylated doxorubicin) c. Tubulin disrupting agents (for example, vincristine, vinblastine) d. Rituximab e. Gemcitabine f. Cytarabine g. Bortezomib h. Histone deacetylase inhibitors This eligibility criterion does not apply to patients who agree to baseline (pre-treatment) imaging only. Concurrent radiation therapy is permissible. - AST and ALT less than 3 X upper limit of normal, unless attributed to tumor, obtained within 2 weeks prior to registration. - Serum creatinine less than 2.0 mg/dL, obtained within 2 weeks prior to registration. Exclusion criteria: - End-stage liver disease unrelated to tumor. - Known active or chronic hepatitis B or hepatitis C infection. - History of iodine hypersensitivity. - Chronic renal insufficiency requiring dialysis. - Women who are pregnant or breast feeding. - Foreseen inability to comply with study requirements.
1.Baselin Scan: a. thyroid protection will begin 24hours before b. extra dose of KI then I-FIAU 2mCi will be administered c. FIAU-PET-CT will be done 2-4 hours after I-FIAU d. begin chemotherapy less than / equal to 3weeks after FIAU-PET-CT 2.Scan after cycle 1 chemotherapy: * thyroid protection continues until 2 weeks after last I-FIAU GroupA a. 1-3 days after chemotherapy, I-FIAU 2mCi will be given (preceded by extra dose KI) b. FIAU-PET-CT will be done 2â??4 hours after I-FIAU Group B a. 1-3 days after chemotherapy, I-FIAU 2mCi will be given (preceded by extra dose KI) b. FIAU-PET-CT will be done 2â??4 hours after I-FIAU c. FIAU-PET-CT will be done 24 (+/-6)hours after I-FIAU, and/or 48 (+/-6) hours after I-FIAU
05/29/2016 05:03 AM