Potential role of 68Ga- and 177Lu-cyclic pentapeptides for in-vivo targeting CXCR4 receptor expression in chemotherapy relapse MCL patient

TL;DR

This paper explores using radiolabeled cyclic pentapeptides to target CXCR4 receptors in a mantle cell lymphoma patient who relapsed after chemotherapy.

Contribution

The development of a theragnostic complex using 68Ga- and 177Lu-cyclic pentapeptides for in-vivo targeting of CXCR4 receptor expression.

Findings

Diagnostic imaging showed high tracer avidity in the mesenteric mass at the L4 level.

Dosimetry studies identified the kidneys as the critical organ with a maximum residence time of 5.39 hours.

CXCR4 receptor expression was confirmed in 86.11% of the cell population in the biopsy sample.

Abstract

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.

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.

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.

Theragnostic complex of radiolabelled 68Ga/177Lu- cyclic pentapeptides have the potential to in-vivo target the CXCR4 receptor expression.

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