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W R Potter

Publications and source records attributed to W R Potter.

34 records · Page 2Linked to original sources
PubMed1987

The theory of photodynamic therapy dosimetry: consequences of photo-destruction of sensitizer.

Photodynamic dose is defined as the area under the curve of sensitizer level plotted as a function of light dose. This is a photochemical definition of dose. We will show that this definition is useful in predicting photobiological response. The photodestruction of sensitizer during photodynamic therapy is shown to result in an upper limit on the photodynamic dose which can be delivered by an unlimited light dose. This limit results in the opportunity to make total photodynamic dose uniform to considerable depths (one to two centimeters). The existence of thresholds for permanent tissue damage allows protection of normal tissue from the large light doses required to achieve this limiting dose deep in the tissue. Higher sensitizer levels in the tumor permit tumor destruction while the normal tissues are protected. A clinical trial to determine the proper level of injected dose necessary for these results is required. This theory of photodynamic therapy (PDT) dosimetry is tested in the DBA-SMT experimental mouse tumor system. Combinations of drug and light which are not reciprocal but are nearly equal by this theory are shown to give equivalent tumor control at seven days post treatment. Reciprocal combinations of drug and light fail to give equivalent results when they ae selected using the theory to choose a combination where reciprocity should fail.

Animals↗
PubMed1987

Photodynamic therapy for palliation of locally recurrent breast carcinoma.

Fourteen women with locally recurrent breast carcinoma on the chest wall following mastectomy were given 30 courses of photodynamic therapy (PDT). All patients had been heavily pretreated with conventional modes of therapy (radiation therapy, chemotherapy, hormonal therapy, surgical resection). Twenty-two courses yielded a partial response; two courses yielded a complete response; four courses showed no response; one patient was treated as an adjunct to surgery; and one patient was lost to follow-up. Duration to response was variable, ranging from 6 weeks to 8 months. Several women had chest wall disease controlled for prolonged periods of time using repeated courses of PDT. Two women had re-epithelialization of ulcerated lesions. Complications were minimal and included pain (two patients), sunburn (two), and infection (one). These results suggest that treatment with PDT can aid in local control of chest wall recurrence following mastectomy in selected patients.

Adult↗
PubMed1986

Dihematoporphyrin ether clearance in primate bladders.

The techniques of in vivo tissue fluorescence photometry and chemical extractions of DHE, which have been recently developed in our laboratory, were employed to study DHE uptake and clearance in the primate bladders. Data show these techniques are readily applicable in studying porphyrin uptake and clearance in primate bladders. Quantitatively a correlation between fluorescence values and tissue extracted DHE values is found. Serum clearance and bladder clearance of DHE appeared phasic, but bladder clearance was slower than serum. The significance of these two methods lies in their applications in determination of drug dosimetry and optimum time for photoactivation in clinical photodynamic therapy.

Animals↗
PubMed1985

Whole bladder photodynamic therapy for transitional cell carcinoma of bladder.

Our preliminary studies indicate that the bulb-tip technique for whole bladder photodynamic therapy (PDT) illuminates the entire bladder mucosa and is applicable to the management of superficial transitional cell carcinoma of the bladder. This treatment modality may be an option to patients who are failures to other standard treatments. A randomized clinical study is needed to decide on PDT as a primary treatment of choice for transitional cell carcinoma of the bladder.

Aged↗
PubMed1985

Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy.

The effect of photodynamic therapy (PDT) on tumor growth as well as on tumor cell survival in vitro and in vivo was studied in the EMT-6 and RIF experimental mouse tumor systems. In vitro, RIF cells were more sensitive towards PDT than were EMT-6 cells when incubated with porphyrin (25 micrograms/ml, dihematoporphyrin ether) and subsequently given graded doses of light. In vivo, both tumor types responded to PDT (EMT-6, dihematoporphyrin ether, 7.5 mg/kg; RIF, dihematoporphyrin ether, 10 mg/kg; both followed 24 hr later by 135 J of light at 630 nm/sq cm) with severe vascular disruption and subsequent disappearance of tumor bulk. However, whereas the cure rate for EMT-6 tumors was 90%, it was 0% for RIF tumors. Raising the light dose to 200 J/sq cm resulted in 100% cures for EMT-6 tumors accompanied by damage to the surrounding tissues and 13% cures for RIF tumors. Tumor cell clonogenicity following PDT in vivo was assessed using the in vitro colony formation assay. In both tumors, it was found to be nearly unaffected by PDT if the tumor tissue was excised and explanted immediately following completion of treatment. This indicates that the effect of PDT on tumor cells directly was not sufficient to decrease tumor clonogenicity even at doses which led to total macroscopic tumor destruction. Where the tumors remained in situ following PDT and explantation was delayed for varying lengths of time (1 to 24 hr), tumor cell death occurred rapidly and progressively, indicating that tumor cell damage was expressed only if the cells remained exposed to the in situ environment after treatment. The kinetics and extent of tumor cell death were very similar for both tumor types despite their difference in cure rates. The reduction in tumor clonogenicity at 4 hr post-PDT closely matched that of tumor deprived of oxygen for the same period of time, implying that one of the major factors contributing to tumor destruction may be damage of the tumor circulation and the consequences of treatment-induced changes in tumor physiology.

Animals↗
PubMed1985

Interaction of photodynamic therapy and hyperthermia: tumor response and cell survival studies after treatment of mice in vivo.

The interaction of photodynamic therapy (PDT) and hyperthermia was studied in the radiation-induced-fibrosarcoma experimental mouse tumor system by tumor regrowth experiments as well as in vivo to in vitro cloning assays. In vivo, PDT (Photofrin II, 10 mg/kg i.p.), followed 24 h later by light (135 J/cm2, 630 nm) and/or heat (44 degrees C, 30 min) caused severe vascular damage (congestion of tumor vessels and hemorrhage) and subsequent disappearance of palpable tumor mass. While heat-treated tumors always started to regrow within 2 days of treatment, regrowth if it occurred was delayed to 4-5 days after PDT and 6-7 days following combined treatments. Only PDT followed by heat cured a considerable number of animals (45%), while PDT alone and heat followed by PDT cured less than 10% of animals, and heat alone caused no tumor cures. The various treatments differed in their immediate as well as their delayed effects on tumor clonogenicity when observed over a 24-h period. Tumors treated with PDT showed no immediate changes in clonogenicity, but progressive delayed cell death occurred if tumors remained in situ. Heat alone led to an immediate reduction in the number of clonogenic tumor cells, followed by some additional cell death for 4 h and subsequent recovery of clonogenicity. PDT followed by heat caused markedly potentiated immediate reduction in cell survival which may be the result of direct interaction of heat and PDT damage affecting the tumor cells. Some tumors rapidly progressed to total eradication, whereas others showed delayed survival values similar to those for tumor having received PDT only. In the reverse sequence, heat before PDT, the tumor cell survival kinetics resembled those following heat treatment alone. The comparative lack of effectiveness of this treatment regimen can be explained by the severe tumor hemorrhage caused by the initial heat treatment which reduces the transmission of light essential for the subsequent PDT treatment. This study shows that despite pronounced similarities in the microscopic and macroscopic appearance shortly after treatment by PDT or hyperthermia, these two modalities lead to tumor destruction by different mechanisms. Furthermore the combination of these two modalities in the proper sequence leads to potentiated cytocidal effects on the tumor cells in vivo.

Animals↗
PubMed1984

Photoradiation therapy in advanced carcinoma of the trachea and bronchus.

Photoradiation therapy is a new technique being investigated for the treatment of solid malignant tumors. In this study, 17 patients with advanced, recurrent, biopsy-proven malignant lesions of the trachea or main-stem bronchus were treated by photoradiation therapy. Patients received hematoporphyrin derivative intravenously three days prior to light therapy. The light was delivered from a fiberoptic fiber attached to the output beam of a dye laser (633 +/- 3 nm). The fiber was passed through the large channel of a bronchoscope (Olympus BF 2T). Of the 17 patients, two had no measurable response to the photoradiation therapy, six had partial necrosis of the tumor, seven patients had a greater than 50 percent reduction in the intraluminal volume of tumor, and two were lost to follow-up. Survival ranged from 5 to 210 days (median survival, 40 days). Complications of the treatment were significant in this group of advanced-stage patients and included excessive secretions, fever, pneumonia, and abscess formation.

Adenocarcinoma↗