Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis.
OBJECTIVE
Many anticancer therapies exert their therapeutic effect by inducing apoptosis in target tumors. We evaluated in a Phase I study the safety and the feasibility of (99m)Tc-Annexin V for imaging chemotherapy-induced apoptosis in human cancers immediately after the first course of chemotherapy.


METHODS
Fifteen patients presenting with lung cancer (n = 10), lymphoma (n = 3), or breast cancer (n = 2) underwent (99m)Tc-Annexin V scintigraphy before and within 3 days after their first course of chemotherapy. Tumor response was evaluated by computed tomography and (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scans, 3 months in average after completing the treatment. Median follow-up was 117 days.


RESULTS
In all cases, no tracer uptake was observed before treatment. However, 24-48 h after the first course of chemotherapy, 7 patients who showed (99m)Tc-Annexin V uptake at tumor sites, suggesting apoptosis, had a complete (n = 4) or a partial response (n = 3). Conversely, 6 of the 8 patients who showed no significant posttreatment tumor uptake had a progressive disease. Despite the lack of tracer uptake after treatment, the 2 patients with breast cancer had a partial response. Overall survival and progression-free survival were significantly related to tracer uptake in treated lung cancers and lymphomas (P < 0.05). No serious adverse events were observed.


CONCLUSIONS
Our preliminary results demonstrated the feasibility and the safety of (99m)Tc-Annexin V for imaging apoptosis in human tumors after the first course of chemotherapy. Initial data suggest that early (99m)Tc-Annexin V tumor uptake may be a predictor of response to treatment in-patients with late stage lung cancer and lymphoma.
Belhocine
Tarik
T
Division of Nuclear Medicine, University Hospital of Liège, 4000 Liège, Belgium. tarik.bel@swing.be
Steinmetz
Neil
N
Hustinx
Roland
R
Bartsch
Pierre
P
Jerusalem
Guy
G
Seidel
Laurence
L
Rigo
Pierre
P
Green
Allan
A
D017304:Annexin A5 / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D015993:Life Tables; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D016019:Survival Analysis; D013997:Time Factors; D014055:Tomography, Emission-Computed; D014057:Tomography, X-Ray Computed
D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C417036:technetium Tc 99m annexin V; D019788:Fluorodeoxyglucose F18