Objective(s): High levels of CXCR4 expression in patients with mantle cell lymphoma is associated with poor prognosis. Various molecular techniques used are unable to specify the metastatic disease burden. Cyclic pentapeptides act as CXCR4 antagonists hence are functional markers of in-vivo CXCR4 receptor expression. In this view, the theragnostic complex of radiolabeled ⁶⁸Ga- and ¹⁷⁷Lu-cyclic pentapeptides was developed to in-vivo target the CXCR4 receptor expression.
Methods: Bone marrow aspiration and flow cytometry were performed to examine the fraction of lymphoid cells and immunophenotyping respectively. In-vitro CXCR4 receptor expression in the biopsied sample was determined using immunohistochemistry and flow cytometry molecular techniques. Diagnostic imaging using ⁶⁸Ga-cyclic pentapeptide was performed to check the in-vivo CXCR4 expression in chemotherapy relapse MCL patient. Dosimetry studies in the same patient was performed with different time-point imaging to calculate the residence time and predict the critical organ.
Results: Bone marrow aspiration indicated ~75% atypical lymphoid cells. Flow cytometric immunophenotyping revealed positivity for CD19, CD20, CD79b, Anti-kappa markers. IHC results showed high nuclear positivity. Approximately 86.11% of the cell population showed CXCR4 positive expression. Diagnostic imaging using ⁶⁸Ga-cyclic pentapeptide showed high tracer avidity in the mesenteric mass at L4 level. The avidity of both ⁶⁸Ga- and ¹⁷⁷Lu- cyclic pentapeptide radiotracers was noted in the mesenteric mass at the L4 level. Dosimetry study using ¹⁷⁷Lu-cyclic pentapeptide indicated kidneys as the critical organ with max residence time of 5.39 h.
Conclusion: Theragnostic complex of radiolabelled ⁶⁸Ga/¹⁷⁷Lu- cyclic pentapeptides have the potential to in-vivo target the CXCR4 receptor expression.