# ACTIONS OF HPD AND PHOTORADIATION OF MAMMARY TUMORS

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1989 · $170,967

## Abstract

There is considerable interest for photodynamic therapy (PDT) as a new
treatment modality in cancer patients.  PDT consists of systemic
administration of photosensitizing drugs, e.g., hematoporphyrin derivative
(Hpd) or Photofrin II (enriched in hydrophobic porphyrins in Hpd), allowing
them to accumulate in tumors, and exposing lesions to photoradiation (laser
irradiation at 630 nm).  Encouraging clinical results are seen in breast,
lung, bladder, and head and neck tumors; controlled (protocol) studies are
underway for bladder and lung cancers.  Nevertheless, much research remains
to elucidate the mechanisms producing tumor regression.  There is a need to
define the sites and events leading to cytotoxicity, the porphyrin species
causing photosensitization, and identify and refine factors that can impact
on optimization of therapeutic response.  We are studying two
well-differentiated rodent mammary tumor models, which we characterized
extensively in vivo and in vitro.  In previous studies, we developed an in
vivo-in vitro protocol, using biochemical parameters as indicators of
photosensitization, to assess sites of action; in this model, endogenous
metabolism and its effect on pharmacokinetics occur, providing an
opportunity to extend findings from studies in vitro.  We now have
considerable support for our thesis tht mitochondria are a critical site of
action, with impaired ATP production leading to cellular demise.  We
propose to expand and extend these interesting findings to gain insight on
factors enhancing target organ photosensitivity.  Experiments are proposed
to:  1) ascertain the sites of action and photosensitizing properties of
Photofrin II in the functional in vivo-in vitro assay and study ATP levels
in situ by NMR spectroscopy; 2) further define mitochondrial sites of
action relative to mitochondrial topography; 3) evaluate in depth the role
of oxygen as a factor for photosensitization, its effect on '02 production
and resulting damage; 4) alter membrane lipid composition by dietary means
as one way to enhance photosensitization; 5) assess photosensitivity as
influenced by hormonal perturbations that affect tumor growth, e.g.,
estrogens, ovariectomy, etc., and metabolism such as thyroxine; and 6)
initiate studies of selected perturbations for additivity of enhancing
photosensitization.  Results should provide new insight regarding
mechanisms of actions leading to cytotoxicity and could lead to development
of combined maneuvers to improve the efficacy of PDT.

## Key facts

- **NIH application ID:** 3174428
- **Project number:** 5R01CA036856-06
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** RUSSELL HILF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $170,967
- **Award type:** 5
- **Project period:** 1984-03-15 → 1992-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174428

## Citation

> US National Institutes of Health, RePORTER application 3174428, ACTIONS OF HPD AND PHOTORADIATION OF MAMMARY TUMORS (5R01CA036856-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174428. Licensed CC0.

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