Intratumoral Distribution of [177Lu]Lu-PSMA-617 Over Time and in Relation to Diagnostic Tracers in Animal Models of Prostate Cancer
Örbom, Anders LU
; Strand, Joanna
LU
; Altai, Mohamed
LU
; Zedan, Wahed
LU
; Kristiansson, Amanda
LU
; Ceder, Jens
LU
and Timmermand, Oskar Vilhelmsson
LU
(2024)
In Cancer Biotherapy and Radiopharmaceuticals
- Abstract (Swedish)
- Introduction: Prostate-specific membrane antigen (PSMA) is a target for diagnostic positron emission tomography (PET)-tracers and radiopharmaceutical therapy (RPT), for example, [177Lu]Lu-PSMA-617, in prostate cancer. This autoradiography study investigates [177Lu]Lu-PSMA-617 intratumoral distribution over time, compared with PSMA expression, proliferation (Ki67), and [68Ga]Ga-PSMA-11, [18F]F-PSMA-1007, [18F]-fluorodeoxyglucose, and [18F]-fluorocholine distribution. Mice with LNCaP, 22Rv1, or PC-3 PIP xenografts got [177Lu]Lu-PSMA-617 i.v. Sacrificed 1 h p.i. if coinjected with diagnostic tracers, otherwise at 20 min, 1?2, 12, 24, 48, 72 h, or 2?3 weeks p.i. Cryosectioned tumors imaged by autoradiography, adjacent sections Ki67 or PSMA... (More)
- Introduction: Prostate-specific membrane antigen (PSMA) is a target for diagnostic positron emission tomography (PET)-tracers and radiopharmaceutical therapy (RPT), for example, [177Lu]Lu-PSMA-617, in prostate cancer. This autoradiography study investigates [177Lu]Lu-PSMA-617 intratumoral distribution over time, compared with PSMA expression, proliferation (Ki67), and [68Ga]Ga-PSMA-11, [18F]F-PSMA-1007, [18F]-fluorodeoxyglucose, and [18F]-fluorocholine distribution. Mice with LNCaP, 22Rv1, or PC-3 PIP xenografts got [177Lu]Lu-PSMA-617 i.v. Sacrificed 1 h p.i. if coinjected with diagnostic tracers, otherwise at 20 min, 1?2, 12, 24, 48, 72 h, or 2?3 weeks p.i. Cryosectioned tumors imaged by autoradiography, adjacent sections Ki67 or PSMA stained. Results: Heterogeneous distribution of [177Lu]Lu-PSMA-617 was seen 20 min p.i., with visible overlap between tumor cells, Ki67, PSMA, and radioactivity at 1?2 h p.i. Strongest Ki67-correlation at 48 h, which became negative at 72 h and beyond with some Ki67+/PSMA+ low radioactivity areas. Uptake in necrotic tissue was only observed at 2?3 weeks p.i. PSMA-targeted tracers distributed identically to [177Lu]Lu-PSMA-617 whereas other tracers only had some overlap. Conclusion: Regrowth of the tumor post-[177Lu]Lu-PSMA-617 administration creates Ki67+/PSMA+ areas that have no radioactivity uptake and need additional therapy fractions. The identical intratumoral distribution of [177Lu]Lu-PSMA-617 and PSMA-targeted PET-tracers indicate that these will reveal the areas inside the tumor targeted by RPT at least at 1 h p.i. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/b533349c-ec3b-4d3b-9a17-33106a7b6fd4
- author
- Örbom, Anders
LU
; Strand, Joanna
LU
; Altai, Mohamed
LU
; Zedan, Wahed
LU
; Kristiansson, Amanda
LU
; Ceder, Jens
LU
and Timmermand, Oskar Vilhelmsson
LU
- organization
- publishing date
- 2024-11-27
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Cancer Biotherapy and Radiopharmaceuticals
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- pmid:39605131
- scopus:85213358165
- ISSN
- 1084-9785
- DOI
- 10.1089/cbr.2024.0170
- language
- English
- LU publication?
- yes
- additional info
- doi: 10.1089/cbr.2024.0170
- id
- b533349c-ec3b-4d3b-9a17-33106a7b6fd4
- date added to LUP
- 2024-11-28 13:38:45
- date last changed
- 2025-04-04 14:20:56
@article{b533349c-ec3b-4d3b-9a17-33106a7b6fd4,
abstract = {{Introduction: Prostate-specific membrane antigen (PSMA) is a target for diagnostic positron emission tomography (PET)-tracers and radiopharmaceutical therapy (RPT), for example, [177Lu]Lu-PSMA-617, in prostate cancer. This autoradiography study investigates [177Lu]Lu-PSMA-617 intratumoral distribution over time, compared with PSMA expression, proliferation (Ki67), and [68Ga]Ga-PSMA-11, [18F]F-PSMA-1007, [18F]-fluorodeoxyglucose, and [18F]-fluorocholine distribution. Mice with LNCaP, 22Rv1, or PC-3 PIP xenografts got [177Lu]Lu-PSMA-617 i.v. Sacrificed 1 h p.i. if coinjected with diagnostic tracers, otherwise at 20 min, 1?2, 12, 24, 48, 72 h, or 2?3 weeks p.i. Cryosectioned tumors imaged by autoradiography, adjacent sections Ki67 or PSMA stained. Results: Heterogeneous distribution of [177Lu]Lu-PSMA-617 was seen 20 min p.i., with visible overlap between tumor cells, Ki67, PSMA, and radioactivity at 1?2 h p.i. Strongest Ki67-correlation at 48 h, which became negative at 72 h and beyond with some Ki67+/PSMA+ low radioactivity areas. Uptake in necrotic tissue was only observed at 2?3 weeks p.i. PSMA-targeted tracers distributed identically to [177Lu]Lu-PSMA-617 whereas other tracers only had some overlap. Conclusion: Regrowth of the tumor post-[177Lu]Lu-PSMA-617 administration creates Ki67+/PSMA+ areas that have no radioactivity uptake and need additional therapy fractions. The identical intratumoral distribution of [177Lu]Lu-PSMA-617 and PSMA-targeted PET-tracers indicate that these will reveal the areas inside the tumor targeted by RPT at least at 1 h p.i.}},
author = {{Örbom, Anders and Strand, Joanna and Altai, Mohamed and Zedan, Wahed and Kristiansson, Amanda and Ceder, Jens and Timmermand, Oskar Vilhelmsson}},
issn = {{1084-9785}},
language = {{eng}},
month = {{11}},
publisher = {{Mary Ann Liebert, Inc.}},
series = {{Cancer Biotherapy and Radiopharmaceuticals}},
title = {{Intratumoral Distribution of [177Lu]Lu-PSMA-617 Over Time and in Relation to Diagnostic Tracers in Animal Models of Prostate Cancer}},
url = {{http://dx.doi.org/10.1089/cbr.2024.0170}},
doi = {{10.1089/cbr.2024.0170}},
year = {{2024}},
}